rs3217754

Variant names:

• chr4-121825130-TC-T
• rs3217754
• NM_176824.3:c.*729delG

Your query was ambiguous. Multiple possible variants found:

• chr4-121825130-TC-T
• chr4-121825130-TC-TCC

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 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: Labcorp Genetics (formerly Invitae), Genomics England PanelApp, G2P
• BBS7-related 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 -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_176824.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BBS7	NM_176824.3	MANE Select	c.*729delG		3_prime_UTR	Exon 19 of 19	NP_789794.1	Q8IWZ6-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BBS7	ENST00000264499.9	TSL:1 MANE Select	c.*729delG		3_prime_UTR	Exon 19 of 19	ENSP00000264499.4	Q8IWZ6-1
	BBS7	ENST00000888033.1		c.*729delG		3_prime_UTR	Exon 19 of 19	ENSP00000558092.1
	BBS7	ENST00000888034.1		c.*729delG		3_prime_UTR	Exon 19 of 19	ENSP00000558093.1

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.500 AC: 3 AN: 6

Other (OTH) AC: 0 AN: 0

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

African (AFR) AF: 0.0777 AC: 3228 AN: 41518

American (AMR) AF: 0.406 AC: 6189 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.355 AC: 1231 AN: 3470

East Asian (EAS) AF: 0.438 AC: 2271 AN: 5182

South Asian (SAS) AF: 0.339 AC: 1631 AN: 4810

European-Finnish (FIN) AF: 0.403 AC: 4248 AN: 10536

Middle Eastern (MID) AF: 0.320 AC: 94 AN: 294

European-Non Finnish (NFE) AF: 0.378 AC: 25671 AN: 67954

Other (OTH) AF: 0.305 AC: 645 AN: 2112

Alfa AF: 0.324 Hom.: 1073

Bravo AF: 0.290

Asia WGS AF: 0.363 AC: 1266 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Bardet-Biedl syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.70
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: rs3217754; hg19: chr4-122746285; COSMIC: COSV52654039; COSMIC: COSV52654039;