rs55803709

Variant names:

• chr4-121835119-G-T
• rs55803709
• NM_176824.3:c.1511+25C>A

Variant summary

Our verdict is Benign. The variant received -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:3
• Conservation: PhyloP100: -0.517
• Publications: 3 publications found

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 Gene-Disease associations (from GenCC):

• Bardet-Biedl syndrome 7

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae), Genomics England PanelApp
• ciliopathy

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• Bardet-Biedl syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 VariationId is 262918.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• 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 rank	MANE	Protein	UniProt
BBS7	NM_176824.3	c.1511+25C>A		intron_variant	Intron 14 of 18	ENST00000264499.9	NP_789794.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BBS7	ENST00000264499.9	c.1511+25C>A		intron_variant	Intron 14 of 18	1	NM_176824.3	ENSP00000264499.4
BBS7	ENST00000506636.1	c.1511+25C>A		intron_variant	Intron 14 of 17	1		ENSP00000423626.1

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

GnomAD2 exomes AF: 0.0341 AC: 8574 AN: 251128 AF XY: 0.0290

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 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

African (AFR) AF: 0.249 AC: 8309 AN: 33368

American (AMR) AF: 0.0275 AC: 1229 AN: 44690

Ashkenazi Jewish (ASJ) AF: 0.0512 AC: 1336 AN: 26098

East Asian (EAS) AF: 0.0244 AC: 968 AN: 39660

South Asian (SAS) AF: 0.00630 AC: 543 AN: 86188

European-Finnish (FIN) AF: 0.00519 AC: 277 AN: 53398

Middle Eastern (MID) AF: 0.0460 AC: 265 AN: 5762

European-Non Finnish (NFE) AF: 0.0178 AC: 19773 AN: 1110328

Other (OTH) AF: 0.0366 AC: 2209 AN: 60310

GnomAD4 genome AF: 0.0834 AC: 12683 AN: 151998 Hom.: 1277 Cov.: 32 AF XY: 0.0802 AC XY: 5959 AN XY: 74308

African (AFR) AF: 0.241 AC: 10000 AN: 41468

American (AMR) AF: 0.0507 AC: 774 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.0461 AC: 160 AN: 3470

East Asian (EAS) AF: 0.0284 AC: 147 AN: 5180

South Asian (SAS) AF: 0.00688 AC: 33 AN: 4800

European-Finnish (FIN) AF: 0.00481 AC: 51 AN: 10594

Middle Eastern (MID) AF: 0.0822 AC: 24 AN: 292

European-Non Finnish (NFE) AF: 0.0195 AC: 1326 AN: 67918

Other (OTH) AF: 0.0778 AC: 164 AN: 2108

Alfa AF: 0.0505 Hom.: 216

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

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 18, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified Benign:1

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.0
DANN	Benign	0.59
PhyloP100		-0.52
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs55803709; hg19: chr4-122756274;