4-121828281-G-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_176824.3(BBS7):c.1891-12C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.744 in 1,609,298 control chromosomes in the GnomAD database, including 447,429 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.79 ( 47679 hom., cov: 33)

Exomes 𝑓: 0.74 ( 399750 hom. )

Consequence

BBS7
NM_176824.3 intron

Scores

Splicing: ADA: 0.0005898

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: -3.27

Publications

10 publications found

Variant links:

Genes affected

BBS7 (HGNC:18758): (Bardet-Biedl syndrome 7) This gene encodes one of eight proteins that form the BBSome complex containing BBS1, BBS2, BBS4, BBS5, BBS7, BBS8, BBS9 and BBIP10. The BBSome complex is believed to recruit Rab8(GTP) to the primary cilium and promote ciliogenesis. The BBSome complex assembly is mediated by a complex composed of three chaperonin-like BBS proteins (BBS6, BBS10, and BBS12) and CCT/TRiC family chaperonins. Mutations in this gene are implicated in Bardet-Biedl syndrome, a genetic disorder whose symptoms include obesity, retinal degeneration, polydactyly and nephropathy; however, mutations in this gene and the BBS8 gene are thought to play a minor role and mutations in chaperonin-like BBS genes are found to be a major contributor to disease development in a multiethnic Bardet-Biedl syndrome patient population. Two transcript variants encoding distinct isoforms have been identified for this gene.[provided by RefSeq, Oct 2014]

BBS7 Gene-Disease associations (from GenCC):

Bardet-Biedl syndrome 7
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae), Genomics England PanelApp
ciliopathy
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
Bardet-Biedl syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

BBS7 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 4-121828281-G-T is Benign according to our data. Variant chr4-121828281-G-T is described in ClinVar as Benign. ClinVar VariationId is 262922.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.884 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BBS7	NM_176824.3 link	c.1891-12C>A		intron_variant	Intron 17 of 18	ENST00000264499.9	NP_789794.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
BBS7	ENST00000264499.9 link	c.1891-12C>A	intron_variant	Intron 17 of 18	1	NM_176824.3	ENSP00000264499.4
BBS7	ENST00000506636.1 link	c.1891-12C>A	intron_variant	Intron 17 of 17	1		ENSP00000423626.1
BBS7	ENST00000507814.5 link	c.160-12C>A	intron_variant	Intron 2 of 4	3		ENSP00000423250.1

Frequencies

GnomAD3 genomes

AF:

0.788

AC:

119810

AN:

151994

Hom.:

47624

Cov.:

show subpopulations

Gnomad AFR

AF:

0.892

Gnomad AMI

AF:

0.632

Gnomad AMR

AF:

0.811

Gnomad ASJ

AF:

0.722

Gnomad EAS

AF:

0.862

Gnomad SAS

AF:

0.734

Gnomad FIN

AF:

0.794

Gnomad MID

AF:

0.748

Gnomad NFE

AF:

0.724

Gnomad OTH

AF:

0.749

GnomAD2 exomes

AF:

0.769

AC:

192361

AN:

250006

AF XY:

0.759

show subpopulations

Gnomad AFR exome

AF:

0.893

Gnomad AMR exome

AF:

0.869

Gnomad ASJ exome

AF:

0.718

Gnomad EAS exome

AF:

0.859

Gnomad FIN exome

AF:

0.792

Gnomad NFE exome

AF:

0.722

Gnomad OTH exome

AF:

0.748

GnomAD4 exome

AF:

0.739

AC:

1077018

AN:

1457184

Hom.:

399750

Cov.:

AF XY:

0.737

AC XY:

534543

AN XY:

725148

show subpopulations

African (AFR)

AF:

0.894

AC:

29832

AN:

33356

American (AMR)

AF:

0.861

AC:

38450

AN:

44642

Ashkenazi Jewish (ASJ)

AF:

0.716

AC:

18689

AN:

26098

East Asian (EAS)

AF:

0.860

AC:

34056

AN:

39590

South Asian (SAS)

AF:

0.721

AC:

62053

AN:

86114

European-Finnish (FIN)

AF:

0.797

AC:

42506

AN:

53300

Middle Eastern (MID)

AF:

0.704

AC:

4052

AN:

5754

European-Non Finnish (NFE)

AF:

0.724

AC:

802599

AN:

1108086

Other (OTH)

AF:

0.743

AC:

44781

AN:

60244

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

12780

25559

38339

51118

63898

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

19972

39944

59916

79888

99860

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.788

AC:

119926

AN:

152114

Hom.:

47679

Cov.:

AF XY:

0.792

AC XY:

58890

AN XY:

74348

show subpopulations

African (AFR)

AF:

0.892

AC:

37010

AN:

41510

American (AMR)

AF:

0.812

AC:

12412

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.722

AC:

2505

AN:

3470

East Asian (EAS)

AF:

0.861

AC:

4459

AN:

5176

South Asian (SAS)

AF:

0.734

AC:

3543

AN:

4824

European-Finnish (FIN)

AF:

0.794

AC:

8394

AN:

10570

Middle Eastern (MID)

AF:

0.735

AC:

216

AN:

294

European-Non Finnish (NFE)

AF:

0.724

AC:

49224

AN:

67954

Other (OTH)

AF:

0.750

AC:

1588

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1341

2682

4023

5364

6705

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

868

1736

2604

3472

4340

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.752

Hom.:

12450

Bravo

AF:

0.792

Asia WGS

AF:

0.788

AC:

2741

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

Bardet-Biedl syndrome 7

Benign:2

Jul 14, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.

Bardet-Biedl syndrome 1

Benign:2

Sep 21, 2015

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

Nov 10, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Bardet-Biedl syndrome

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.055

(source)

DANN

Benign

0.54

PhyloP100

-3.3

PromoterAI

0.00060

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00059

dbscSNV1_RF

Benign

0.020

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over