4-121825130-TC-T

Position:

• chr4-121825130-TC-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_176824.3(BBS7):​c.*729delG variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.30 (8338 hom., cov: 19)
  • Exomes 𝑓: 0.50 (1 hom.)
• Consequence: BBS7 NM_176824.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.698

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 -10 ACMG points.

• BP6: Variant 4-121825130-TC-T is Benign according to our data. Variant chr4-121825130-TC-T is described in ClinVar as [Benign]. Clinvar id is 347471.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.423 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BBS7	NM_176824.3	c.*729delG		3_prime_UTR_variant	19/19	ENST00000264499.9	NP_789794.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BBS7	ENST00000264499	c.*729delG		3_prime_UTR_variant	19/19	1	NM_176824.3	ENSP00000264499.4
BBS7	ENST00000507814	c.*110delG		3_prime_UTR_variant	5/5	3		ENSP00000423250.1

Frequencies

GnomAD3 genomes AF: 0.300 AC: 45556 AN: 151912 Hom.: 8330 Cov.: 19

Gnomad AFR AF: 0.0779

Gnomad AMI AF: 0.400

Gnomad AMR AF: 0.405

Gnomad ASJ AF: 0.355

Gnomad EAS AF: 0.439

Gnomad SAS AF: 0.338

Gnomad FIN AF: 0.403

Gnomad MID AF: 0.329

Gnomad NFE AF: 0.378

Gnomad OTH AF: 0.304

GnomAD4 exome AF: 0.500 AC: 3 AN: 6 Hom.: 1 Cov.: 0 AF XY: 0.500 AC XY: 3 AN XY: 6

Gnomad4 NFE exome AF: 0.500

GnomAD4 genome AF: 0.300 AC: 45572 AN: 152032 Hom.: 8338 Cov.: 19 AF XY: 0.304 AC XY: 22591 AN XY: 74298

Gnomad4 AFR AF: 0.0777

Gnomad4 AMR AF: 0.406

Gnomad4 ASJ AF: 0.355

Gnomad4 EAS AF: 0.438

Gnomad4 SAS AF: 0.339

Gnomad4 FIN AF: 0.403

Gnomad4 NFE AF: 0.378

Gnomad4 OTH AF: 0.305

Alfa AF: 0.324 Hom.: 1073

Bravo AF: 0.290

Asia WGS AF: 0.363 AC: 1266 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Bardet-Biedl syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

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: rs3217754; hg19: chr4-122746285;