rs3217753

Variant names:

• chr4-121825170-A-G
• rs3217753
• NM_176824.3:c.*690T>C

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.*690T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.271 in 152,174 control chromosomes in the GnomAD database, including 6,211 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.27 (6210 hom., cov: 32)
  • Exomes 𝑓: 0.29 (1 hom.)
• Consequence: BBS7 NM_176824.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.802
• Publications: 14 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 4-121825170-A-G is Benign according to our data. Variant chr4-121825170-A-G is described in ClinVar as Benign. ClinVar VariationId is 347473.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.

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.*690T>C		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.*690T>C		3_prime_UTR	Exon 19 of 19	ENSP00000264499.4	Q8IWZ6-1
	BBS7	ENST00000888033.1		c.*690T>C		3_prime_UTR	Exon 19 of 19	ENSP00000558092.1
	BBS7	ENST00000888034.1		c.*690T>C		3_prime_UTR	Exon 19 of 19	ENSP00000558093.1

Frequencies

GnomAD3 genomes AF: 0.271 AC: 41200 AN: 152014 Hom.: 6207 Cov.: 32

Gnomad AFR AF: 0.150

Gnomad AMI AF: 0.227

Gnomad AMR AF: 0.304

Gnomad ASJ AF: 0.316

Gnomad EAS AF: 0.196

Gnomad SAS AF: 0.303

Gnomad FIN AF: 0.378

Gnomad MID AF: 0.297

Gnomad NFE AF: 0.323

Gnomad OTH AF: 0.275

GnomAD4 exome AF: 0.286 AC: 12 AN: 42 Hom.: 1 Cov.: 0 AF XY: 0.385 AC XY: 10 AN XY: 26

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AF: 0.500 AC: 1 AN: 2

East Asian (EAS) AF: 0.00 AC: 0 AN: 2

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.250 AC: 8 AN: 32

Other (OTH) AF: 0.750 AC: 3 AN: 4

GnomAD4 genome AF: 0.271 AC: 41215 AN: 152132 Hom.: 6210 Cov.: 32 AF XY: 0.274 AC XY: 20400 AN XY: 74344

African (AFR) AF: 0.150 AC: 6209 AN: 41528

American (AMR) AF: 0.304 AC: 4641 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.316 AC: 1095 AN: 3468

East Asian (EAS) AF: 0.197 AC: 1017 AN: 5174

South Asian (SAS) AF: 0.302 AC: 1461 AN: 4830

European-Finnish (FIN) AF: 0.378 AC: 3985 AN: 10548

Middle Eastern (MID) AF: 0.289 AC: 85 AN: 294

European-Non Finnish (NFE) AF: 0.323 AC: 21932 AN: 67986

Other (OTH) AF: 0.276 AC: 583 AN: 2114

Alfa AF: 0.308 Hom.: 6670

Bravo AF: 0.257

Asia WGS AF: 0.230 AC: 799 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Bardet-Biedl syndrome 7 (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	8.3
DANN	Benign	0.61
PhyloP100		0.80
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: rs3217753; hg19: chr4-122746325;