rs111713350

chr4-121848809-CTCTT-Cchr4-121848809-CTCTT-CTCTTTCTT

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_176824.3(BBS7):c.934+31_934+34del variant causes a intron change. The variant allele was found at a frequency of 0.0391 in 1,544,376 control chromosomes in the GnomAD database, including 6,682 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.13 (3373 hom., cov: 30)
  • Exomes 𝑓: 0.029 (3309 hom.)
• Consequence: BBS7 NM_176824.3 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 3.88

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 -16 ACMG points.

• BP6: Variant 4-121848809-CTCTT-C is Benign according to our data. Variant chr4-121848809-CTCTT-C is described in ClinVar as [Likely_benign]. Clinvar id is 262923.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-121848809-CTCTT-C is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.39 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BBS7	NM_176824.3	c.934+31_934+34del		intron_variant		ENST00000264499.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BBS7	ENST00000264499.9	c.934+31_934+34del		intron_variant		1	NM_176824.3	P1
BBS7	ENST00000506636.1	c.934+31_934+34del		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.128 AC: 19370 AN: 151826 Hom.: 3362 Cov.: 30

Gnomad AFR AF: 0.395

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.0694

Gnomad ASJ AF: 0.0502

Gnomad EAS AF: 0.0277

Gnomad SAS AF: 0.00725

Gnomad FIN AF: 0.00511

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0204

Gnomad OTH AF: 0.113

GnomAD3 exomes AF: 0.0467 AC: 11618 AN: 248794 Hom.: 1477 AF XY: 0.0383 AC XY: 5153 AN XY: 134396

Gnomad AFR exome AF: 0.406

Gnomad AMR exome AF: 0.0328

Gnomad ASJ exome AF: 0.0547

Gnomad EAS exome AF: 0.0307

Gnomad SAS exome AF: 0.00644

Gnomad FIN exome AF: 0.00397

Gnomad NFE exome AF: 0.0203

Gnomad OTH exome AF: 0.0404

GnomAD4 exome AF: 0.0295 AC: 41012 AN: 1392432 Hom.: 3309 AF XY: 0.0276 AC XY: 19258 AN XY: 696846

Gnomad4 AFR exome AF: 0.416

Gnomad4 AMR exome AF: 0.0370

Gnomad4 ASJ exome AF: 0.0554

Gnomad4 EAS exome AF: 0.0244

Gnomad4 SAS exome AF: 0.00696

Gnomad4 FIN exome AF: 0.00521

Gnomad4 NFE exome AF: 0.0186

Gnomad4 OTH exome AF: 0.0481

GnomAD4 genome AF: 0.128 AC: 19422 AN: 151944 Hom.: 3373 Cov.: 30 AF XY: 0.123 AC XY: 9132 AN XY: 74298

Gnomad4 AFR AF: 0.395

Gnomad4 AMR AF: 0.0691

Gnomad4 ASJ AF: 0.0502

Gnomad4 EAS AF: 0.0280

Gnomad4 SAS AF: 0.00684

Gnomad4 FIN AF: 0.00511

Gnomad4 NFE AF: 0.0204

Gnomad4 OTH AF: 0.112

Alfa AF: 0.0704 Hom.: 256

Bravo AF: 0.148

Asia WGS AF: 0.0400 AC: 139 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 18, 2021

- -

Computational scores

Source: dbNSFP v4.3

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: rs111713350; hg19: chr4-122769964;