rs55803709

chr4-121835119-G-T

Variant summary

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

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.517

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=-0.9).
• 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	UniProt
BBS7	NM_176824.3	c.1511+25C>A		intron_variant		ENST00000264499.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BBS7	ENST00000264499.9	c.1511+25C>A		intron_variant		1	NM_176824.3	P1
BBS7	ENST00000506636.1	c.1511+25C>A		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.0833 AC: 12654 AN: 151880 Hom.: 1272 Cov.: 32

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

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.: 30 AF XY: 0.0229 AC XY: 16620 AN XY: 726364

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.: 32 AF XY: 0.0802 AC XY: 5959 AN XY: 74308

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:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

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- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 18, 2021

- -

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

Other links and lift over

dbSNP: rs55803709; hg19: chr4-122756274;