4-121828386-C-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.1890+16G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.342 in 1,603,450 control chromosomes in the GnomAD database, including 97,057 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.40 ( 12929 hom., cov: 33)

Exomes 𝑓: 0.34 ( 84128 hom. )

Consequence

BBS7
NM_176824.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -0.421

Publications

27 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, Genomics England PanelApp, Labcorp Genetics (formerly Invitae)
BBS7-related 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=-0.86).

BP6

Variant 4-121828386-C-T is Benign according to our data. Variant chr4-121828386-C-T is described in ClinVar as Benign. ClinVar VariationId is 262921.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.539 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_176824.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BBS7	NM_176824.3	MANE Select	c.1890+16G>A		intron	N/A	NP_789794.1	Q8IWZ6-1
	BBS7	NM_018190.4		c.1890+16G>A		intron	N/A	NP_060660.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
BBS7	ENST00000264499.9	TSL:1 MANE Select	c.1890+16G>A	intron	N/A	ENSP00000264499.4	Q8IWZ6-1
BBS7	ENST00000506636.1	TSL:1	c.1890+16G>A	intron	N/A	ENSP00000423626.1	Q8IWZ6-2
BBS7	ENST00000888033.1		c.1938+16G>A	intron	N/A	ENSP00000558092.1

Frequencies

GnomAD3 genomes

AF:

0.399

AC:

60610

AN:

151900

Hom.:

12909

Cov.:

show subpopulations

Gnomad AFR

AF:

0.545

Gnomad AMI

AF:

0.231

Gnomad AMR

AF:

0.373

Gnomad ASJ

AF:

0.366

Gnomad EAS

AF:

0.226

Gnomad SAS

AF:

0.310

Gnomad FIN

AF:

0.384

Gnomad MID

AF:

0.383

Gnomad NFE

AF:

0.343

Gnomad OTH

AF:

0.383

GnomAD2 exomes

AF:

0.350

AC:

87778

AN:

251146

AF XY:

0.345

show subpopulations

Gnomad AFR exome

AF:

0.547

Gnomad AMR exome

AF:

0.343

Gnomad ASJ exome

AF:

0.368

Gnomad EAS exome

AF:

0.228

Gnomad FIN exome

AF:

0.377

Gnomad NFE exome

AF:

0.343

Gnomad OTH exome

AF:

0.332

GnomAD4 exome

AF:

0.336

AC:

488145

AN:

1451432

Hom.:

84128

Cov.:

AF XY:

0.337

AC XY:

243457

AN XY:

722760

show subpopulations

African (AFR)

AF:

0.552

AC:

18341

AN:

33230

American (AMR)

AF:

0.348

AC:

15566

AN:

44696

Ashkenazi Jewish (ASJ)

AF:

0.374

AC:

9762

AN:

26072

East Asian (EAS)

AF:

0.210

AC:

8318

AN:

39560

South Asian (SAS)

AF:

0.326

AC:

28066

AN:

86032

European-Finnish (FIN)

AF:

0.370

AC:

19766

AN:

53382

Middle Eastern (MID)

AF:

0.333

AC:

1914

AN:

5740

European-Non Finnish (NFE)

AF:

0.332

AC:

366190

AN:

1102686

Other (OTH)

AF:

0.337

AC:

20222

AN:

60034

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

16796

33593

50389

67186

83982

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

11672

23344

35016

46688

58360

<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:

0.399

AC:

60676

AN:

152018

Hom.:

12929

Cov.:

AF XY:

0.398

AC XY:

29551

AN XY:

74302

show subpopulations

African (AFR)

AF:

0.545

AC:

22578

AN:

41456

American (AMR)

AF:

0.372

AC:

5691

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.366

AC:

1270

AN:

3468

East Asian (EAS)

AF:

0.227

AC:

1175

AN:

5178

South Asian (SAS)

AF:

0.309

AC:

1490

AN:

4828

European-Finnish (FIN)

AF:

0.384

AC:

4058

AN:

10554

Middle Eastern (MID)

AF:

0.384

AC:

113

AN:

294

European-Non Finnish (NFE)

AF:

0.343

AC:

23284

AN:

67938

Other (OTH)

AF:

0.383

AC:

806

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1803

3606

5409

7212

9015

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

564

1128

1692

2256

2820

<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:

0.363

Hom.:

14394

Bravo

AF:

0.404

Asia WGS

AF:

0.270

AC:

937

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Bardet-Biedl syndrome 1 (2)

not provided (2)

Bardet-Biedl syndrome (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

1.0

(source)

DANN

Benign

0.48

PhyloP100

-0.42

PromoterAI

-0.020

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over