rs56159666

chr4-121861724-G-A

Variant summary

Our verdict is Benign. Variant got -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:2
• Conservation: PhyloP100: -0.239

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 -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 id is 262919.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-121861724-G-A is described in Lovd as [Benign].
• 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/exons	MANE	UniProt
BBS7	NM_176824.3	c.166-45C>T		intron_variant		ENST00000264499.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BBS7	ENST00000264499.9	c.166-45C>T		intron_variant		1	NM_176824.3	P1
BBS7	ENST00000506636.1	c.166-45C>T		intron_variant		1
BBS7	ENST00000502444.1	n.340-45C>T		intron_variant, non_coding_transcript_variant		2
BBS7	ENST00000505692.1			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

GnomAD3 exomes AF: 0.305 AC: 73192 AN: 240332 Hom.: 11465 AF XY: 0.308 AC XY: 40272 AN XY: 130758

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 SAS exome AF: 0.323

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

Gnomad4 AFR exome AF: 0.137

Gnomad4 AMR exome AF: 0.311

Gnomad4 ASJ exome AF: 0.319

Gnomad4 EAS exome AF: 0.185

Gnomad4 SAS exome AF: 0.319

Gnomad4 FIN exome AF: 0.365

Gnomad4 NFE exome AF: 0.314

Gnomad4 OTH exome AF: 0.290

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

Gnomad4 AFR AF: 0.147

Gnomad4 AMR AF: 0.304

Gnomad4 ASJ AF: 0.315

Gnomad4 EAS AF: 0.198

Gnomad4 SAS AF: 0.301

Gnomad4 FIN AF: 0.381

Gnomad4 NFE AF: 0.322

Gnomad4 OTH AF: 0.276

Alfa AF: 0.313 Hom.: 1422

Bravo AF: 0.256

Asia WGS AF: 0.228 AC: 792 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 10, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	6.3
Dann	Benign	0.72

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

Publications

LitVar

Other links and lift over

dbSNP: rs56159666; hg19: chr4-122782879;