Variant 4-121848812-T-C 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.934+32A>G variant causes a intron change. The variant allele was found at a frequency of 0.252 in 1,476,652 control chromosomes in the GnomAD database, including 46,546 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.26 ( 3867 hom., cov: 30)

Exomes 𝑓: 0.25 ( 42679 hom. )

Consequence

BBS7
NM_176824.3 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 3.88

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=-0.77).

BP6

Variant 4-121848812-T-C is Benign according to our data. Variant chr4-121848812-T-C is described in ClinVar as [Benign]. Clinvar id is 262924.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-121848812-T-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.263 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.934+32A>G		intron_variant		ENST00000264499.9	NP_789794.1	Q8IWZ6-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BBS7	ENST00000264499.9 linkuse as main transcript	c.934+32A>G		intron_variant		1	NM_176824.3	ENSP00000264499.4		Q8IWZ6-1
BBS7	ENST00000506636.1 linkuse as main transcript	c.934+32A>G		intron_variant		1		ENSP00000423626.1		Q8IWZ6-2

Frequencies

GnomAD3 genomes

AF:

0.256

AC:

31826

AN:

124484

Hom.:

3866

Cov.:

show subpopulations

Gnomad AFR

AF:

0.224

Gnomad AMI

AF:

0.216

Gnomad AMR

AF:

0.266

Gnomad ASJ

AF:

0.278

Gnomad EAS

AF:

0.158

Gnomad SAS

AF:

0.150

Gnomad FIN

AF:

0.323

Gnomad MID

AF:

0.205

Gnomad NFE

AF:

0.266

Gnomad OTH

AF:

0.259

GnomAD3 exomes

AF:

0.231

AC:

57577

AN:

249166

Hom.:

7161

AF XY:

0.230

AC XY:

31016

AN XY:

134636

show subpopulations

Gnomad AFR exome

AF:

0.0940

Gnomad AMR exome

AF:

0.246

Gnomad ASJ exome

AF:

0.257

Gnomad EAS exome

AF:

0.153

Gnomad SAS exome

AF:

0.163

Gnomad FIN exome

AF:

0.314

Gnomad NFE exome

AF:

0.260

Gnomad OTH exome

AF:

0.224

GnomAD4 exome

AF:

0.252

AC:

340466

AN:

1352126

Hom.:

42679

Cov.:

AF XY:

0.250

AC XY:

169342

AN XY:

677476

show subpopulations

Gnomad4 AFR exome

AF:

0.222

Gnomad4 AMR exome

AF:

0.260

Gnomad4 ASJ exome

AF:

0.284

Gnomad4 EAS exome

AF:

0.139

Gnomad4 SAS exome

AF:

0.167

Gnomad4 FIN exome

AF:

0.310

Gnomad4 NFE exome

AF:

0.260

Gnomad4 OTH exome

AF:

0.240

GnomAD4 genome

AF:

0.256

AC:

31823

AN:

124526

Hom.:

3867

Cov.:

AF XY:

0.256

AC XY:

15720

AN XY:

61368

show subpopulations

Gnomad4 AFR

AF:

0.224

Gnomad4 AMR

AF:

0.266

Gnomad4 ASJ

AF:

0.278

Gnomad4 EAS

AF:

0.158

Gnomad4 SAS

AF:

0.148

Gnomad4 FIN

AF:

0.323

Gnomad4 NFE

AF:

0.266

Gnomad4 OTH

AF:

0.257

Alfa

AF:

0.235

Hom.:

665

Bravo

AF:

0.198

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

-0.77

CADD

Benign

DANN

Benign

0.84

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