rs56159666

Variant names:

• chr4-121861724-G-A
• rs56159666
• NM_176824.3:c.166-45C>T

Your query was ambiguous. Multiple possible variants found:

• chr4-121861724-G-A
• chr4-121861724-G-T

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.166-45C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.304 in 1,599,604 control chromosomes in the GnomAD database, including 76,088 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.27 (6192 hom., cov: 32)
  • Exomes 𝑓: 0.31 (69896 hom.)
• Consequence: BBS7 NM_176824.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.239
• Publications: 7 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=-0.83).
• BP6: Variant 4-121861724-G-A is Benign according to our data. Variant chr4-121861724-G-A is described in ClinVar as Benign. ClinVar VariationId is 262919.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.319 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BBS7	NM_176824.3	c.166-45C>T		intron_variant	Intron 3 of 18	ENST00000264499.9	NP_789794.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BBS7	ENST00000264499.9	c.166-45C>T		intron_variant	Intron 3 of 18	1	NM_176824.3	ENSP00000264499.4
BBS7	ENST00000506636.1	c.166-45C>T		intron_variant	Intron 3 of 17	1		ENSP00000423626.1
BBS7	ENST00000502444.1	n.340-45C>T		intron_variant	Intron 3 of 3	2
BBS7	ENST00000505692.1	n.-45C>T		upstream_gene_variant		2

Frequencies

GnomAD3 genomes AF: 0.271 AC: 41073 AN: 151770 Hom.: 6189 Cov.: 32

Gnomad AFR AF: 0.148

Gnomad AMI AF: 0.227

Gnomad AMR AF: 0.304

Gnomad ASJ AF: 0.315

Gnomad EAS AF: 0.198

Gnomad SAS AF: 0.302

Gnomad FIN AF: 0.381

Gnomad MID AF: 0.299

Gnomad NFE AF: 0.322

Gnomad OTH AF: 0.275

GnomAD2 exomes AF: 0.305 AC: 73192 AN: 240332 AF XY: 0.308

Gnomad AFR exome AF: 0.143

Gnomad AMR exome AF: 0.310

Gnomad ASJ exome AF: 0.314

Gnomad EAS exome AF: 0.197

Gnomad FIN exome AF: 0.373

Gnomad NFE exome AF: 0.324

Gnomad OTH exome AF: 0.294

GnomAD4 exome AF: 0.308 AC: 445409 AN: 1447712 Hom.: 69896 Cov.: 28 AF XY: 0.310 AC XY: 223272 AN XY: 720476

African (AFR) AF: 0.137 AC: 4508 AN: 33008

American (AMR) AF: 0.311 AC: 13751 AN: 44184

Ashkenazi Jewish (ASJ) AF: 0.319 AC: 8288 AN: 25960

East Asian (EAS) AF: 0.185 AC: 7278 AN: 39314

South Asian (SAS) AF: 0.319 AC: 27283 AN: 85456

European-Finnish (FIN) AF: 0.365 AC: 19290 AN: 52788

Middle Eastern (MID) AF: 0.273 AC: 1563 AN: 5732

European-Non Finnish (NFE) AF: 0.314 AC: 346139 AN: 1101486

Other (OTH) AF: 0.290 AC: 17309 AN: 59784

GnomAD4 genome AF: 0.270 AC: 41086 AN: 151892 Hom.: 6192 Cov.: 32 AF XY: 0.274 AC XY: 20354 AN XY: 74228

African (AFR) AF: 0.147 AC: 6110 AN: 41438

American (AMR) AF: 0.304 AC: 4635 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.315 AC: 1094 AN: 3468

East Asian (EAS) AF: 0.198 AC: 1025 AN: 5172

South Asian (SAS) AF: 0.301 AC: 1447 AN: 4804

European-Finnish (FIN) AF: 0.381 AC: 4004 AN: 10522

Middle Eastern (MID) AF: 0.291 AC: 85 AN: 292

European-Non Finnish (NFE) AF: 0.322 AC: 21896 AN: 67918

Other (OTH) AF: 0.276 AC: 583 AN: 2110

Alfa AF: 0.308 Hom.: 1428

Bravo AF: 0.256

Asia WGS AF: 0.228 AC: 792 AN: 3476

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

- -

Nov 10, 2018

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	-0.83
CADD	Benign	6.3
DANN	Benign	0.72
PhyloP100		-0.24
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs56159666; hg19: chr4-122782879;