4-121828386-C-T

Position:

• chr4-121828386-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000264499.9(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 ENST00000264499.9 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -0.421

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]

ACMG classification

Verdict is Benign. Variant got -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 id is 262921.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-121828386-C-T is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.539 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BBS7	NM_176824.3	c.1890+16G>A		intron_variant		ENST00000264499.9	NP_789794.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BBS7	ENST00000264499.9	c.1890+16G>A		intron_variant		1	NM_176824.3	ENSP00000264499	P1
BBS7	ENST00000506636.1	c.1890+16G>A		intron_variant		1		ENSP00000423626
BBS7	ENST00000507814.5	c.159+16G>A		intron_variant		3		ENSP00000423250

Frequencies

GnomAD3 genomes AF: 0.399 AC: 60610 AN: 151900 Hom.: 12909 Cov.: 33

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

GnomAD3 exomes AF: 0.350 AC: 87778 AN: 251146 Hom.: 15948 AF XY: 0.345 AC XY: 46858 AN XY: 135744

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 SAS exome AF: 0.328

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.: 30 AF XY: 0.337 AC XY: 243457 AN XY: 722760

Gnomad4 AFR exome AF: 0.552

Gnomad4 AMR exome AF: 0.348

Gnomad4 ASJ exome AF: 0.374

Gnomad4 EAS exome AF: 0.210

Gnomad4 SAS exome AF: 0.326

Gnomad4 FIN exome AF: 0.370

Gnomad4 NFE exome AF: 0.332

Gnomad4 OTH exome AF: 0.337

GnomAD4 genome AF: 0.399 AC: 60676 AN: 152018 Hom.: 12929 Cov.: 33 AF XY: 0.398 AC XY: 29551 AN XY: 74302

Gnomad4 AFR AF: 0.545

Gnomad4 AMR AF: 0.372

Gnomad4 ASJ AF: 0.366

Gnomad4 EAS AF: 0.227

Gnomad4 SAS AF: 0.309

Gnomad4 FIN AF: 0.384

Gnomad4 NFE AF: 0.343

Gnomad4 OTH AF: 0.383

Alfa AF: 0.355 Hom.: 10710

Bravo AF: 0.404

Asia WGS AF: 0.270 AC: 937 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Bardet-Biedl syndrome 1 Benign:2

Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, criteria provided, single submitter	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	Sep 21, 2015	- -

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 10, 2018	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

Bardet-Biedl syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.0
DANN	Benign	0.48

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

Other links and lift over

dbSNP: rs1507994; hg19: chr4-122749541; COSMIC: COSV52655158; COSMIC: COSV52655158;