Variant chr4-121835119-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_176824.3(BBS7):c.1511+25C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0295 in 1,611,800 control chromosomes in the GnomAD database, including 2,709 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.083 ( 1277 hom., cov: 32)

Exomes 𝑓: 0.024 ( 1432 hom. )

Consequence

BBS7
NM_176824.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.517

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 4-121835119-G-T is Benign according to our data. Variant chr4-121835119-G-T is described in ClinVar as [Benign]. Clinvar id is 262918.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-121835119-G-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.237 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BBS7	NM_176824.3 linkuse as main transcript	c.1511+25C>A		intron_variant		ENST00000264499.9	NP_789794.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BBS7	ENST00000264499.9 linkuse as main transcript	c.1511+25C>A		intron_variant		1	NM_176824.3	ENSP00000264499	P1	Q8IWZ6-1
BBS7	ENST00000506636.1 linkuse as main transcript	c.1511+25C>A		intron_variant		1		ENSP00000423626		Q8IWZ6-2

Frequencies

GnomAD3 genomes

AF:

0.0833

AC:

12654

AN:

151880

Hom.:

1272

Cov.:

show subpopulations

Gnomad AFR

AF:

0.241

Gnomad AMI

AF:

0.00440

Gnomad AMR

AF:

0.0509

Gnomad ASJ

AF:

0.0461

Gnomad EAS

AF:

0.0281

Gnomad SAS

AF:

0.00687

Gnomad FIN

AF:

0.00481

Gnomad MID

AF:

0.0732

Gnomad NFE

AF:

0.0195

Gnomad OTH

AF:

0.0786

GnomAD3 exomes

AF:

0.0341

AC:

8574

AN:

251128

Hom.:

561

AF XY:

0.0290

AC XY:

3940

AN XY:

135712

show subpopulations

Gnomad AFR exome

AF:

0.247

Gnomad AMR exome

AF:

0.0238

Gnomad ASJ exome

AF:

0.0503

Gnomad EAS exome

AF:

0.0307

Gnomad SAS exome

AF:

0.00588

Gnomad FIN exome

AF:

0.00411

Gnomad NFE exome

AF:

0.0194

Gnomad OTH exome

AF:

0.0322

GnomAD4 exome

AF:

0.0239

AC:

34909

AN:

1459802

Hom.:

1432

Cov.:

AF XY:

0.0229

AC XY:

16620

AN XY:

726364

show subpopulations

Gnomad4 AFR exome

AF:

0.249

Gnomad4 AMR exome

AF:

0.0275

Gnomad4 ASJ exome

AF:

0.0512

Gnomad4 EAS exome

AF:

0.0244

Gnomad4 SAS exome

AF:

0.00630

Gnomad4 FIN exome

AF:

0.00519

Gnomad4 NFE exome

AF:

0.0178

Gnomad4 OTH exome

AF:

0.0366

GnomAD4 genome

AF:

0.0834

AC:

12683

AN:

151998

Hom.:

1277

Cov.:

AF XY:

0.0802

AC XY:

5959

AN XY:

74308

show subpopulations

Gnomad4 AFR

AF:

0.241

Gnomad4 AMR

AF:

0.0507

Gnomad4 ASJ

AF:

0.0461

Gnomad4 EAS

AF:

0.0284

Gnomad4 SAS

AF:

0.00688

Gnomad4 FIN

AF:

0.00481

Gnomad4 NFE

AF:

0.0195

Gnomad4 OTH

AF:

0.0778

Alfa

AF:

0.0496

Hom.:

100

Bravo

AF:

0.0950

Asia WGS

AF:

0.0300

AC:

104

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 18, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

1.0

DANN

Benign

0.59

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over