rs35194418

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_176824.3(BBS7):c.186C>T(p.Pro62Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00122 in 1,613,080 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. P62P) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0062 ( 7 hom., cov: 32)

Exomes 𝑓: 0.00071 ( 5 hom. )

Consequence

BBS7
NM_176824.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -1.51

Publications

1 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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.66).

BP6

Variant 4-121861659-G-A is Benign according to our data. Variant chr4-121861659-G-A is described in ClinVar as Benign. ClinVar VariationId is 262920.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.51 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00617 (936/151742) while in subpopulation AFR AF = 0.0203 (839/41352). AF 95% confidence interval is 0.0192. There are 7 homozygotes in GnomAd4. There are 450 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BBS7	NM_176824.3 link	c.186C>T	p.Pro62Pro	synonymous_variant	Exon 4 of 19	ENST00000264499.9	NP_789794.1	Q8IWZ6-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
BBS7	ENST00000264499.9 link	c.186C>T	p.Pro62Pro	synonymous_variant	Exon 4 of 19	1	NM_176824.3	ENSP00000264499.4	Q8IWZ6-1
BBS7	ENST00000506636.1 link	c.186C>T	p.Pro62Pro	synonymous_variant	Exon 4 of 18	1		ENSP00000423626.1	Q8IWZ6-2
BBS7	ENST00000502444.1 link	n.360C>T		non_coding_transcript_exon_variant	Exon 4 of 4	2
BBS7	ENST00000505692.1 link	n.21C>T		non_coding_transcript_exon_variant	Exon 1 of 2	2

Frequencies

GnomAD3 genomes

AF:

0.00616

AC:

934

AN:

151624

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0203

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00309

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000194

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000952

Gnomad MID

AF:

0.00321

Gnomad NFE

AF:

0.000427

Gnomad OTH

AF:

0.00865

GnomAD2 exomes

AF:

0.00179

AC:

450

AN:

251110

AF XY:

0.00140

show subpopulations

Gnomad AFR exome

AF:

0.0215

Gnomad AMR exome

AF:

0.00159

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000272

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.000264

Gnomad OTH exome

AF:

0.00180

GnomAD4 exome

AF:

0.000711

AC:

1039

AN:

1461338

Hom.:

Cov.:

AF XY:

0.000604

AC XY:

439

AN XY:

726962

show subpopulations

African (AFR)

AF:

0.0182

AC:

610

AN:

33460

American (AMR)

AF:

0.00204

AC:

AN:

44702

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26112

East Asian (EAS)

AF:

0.000151

AC:

AN:

39666

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86236

European-Finnish (FIN)

AF:

0.0000187

AC:

AN:

53378

Middle Eastern (MID)

AF:

0.00208

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000182

AC:

202

AN:

1111654

Other (OTH)

AF:

0.00192

AC:

116

AN:

60362

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

101

151

202

252

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

112

140

<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:

0.00617

AC:

936

AN:

151742

Hom.:

Cov.:

AF XY:

0.00607

AC XY:

450

AN XY:

74120

show subpopulations

African (AFR)

AF:

0.0203

AC:

839

AN:

41352

American (AMR)

AF:

0.00309

AC:

AN:

15228

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.000194

AC:

AN:

5152

South Asian (SAS)

AF:

0.00

AC:

AN:

4806

European-Finnish (FIN)

AF:

0.0000952

AC:

AN:

10500

Middle Eastern (MID)

AF:

0.00345

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.000427

AC:

AN:

67932

Other (OTH)

AF:

0.00856

AC:

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

131

174

218

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00256

Hom.:

Bravo

AF:

0.00692

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.000491

EpiControl

AF:

0.000296

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Clinical Genetics, Academic Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Bardet-Biedl syndrome 1

Benign:1

Jun 28, 2017

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

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Bardet-Biedl syndrome

Benign:1

Jan 07, 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

-0.66

CADD

Benign

0.43

(source)

DANN

Benign

0.57

PhyloP100

-1.5

Mutation Taster

=98/2

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

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