rs75847960

chr15-72737433-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_033028.5(BBS4):c.1451-45T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.11 in 1,501,516 control chromosomes in the GnomAD database, including 10,093 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.085 (668 hom., cov: 32)
  • Exomes 𝑓: 0.11 (9425 hom.)
• Consequence: BBS4 NM_033028.5 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:2
• Conservation: PhyloP100: 0.127

Genes affected

BBS4 (HGNC:969): (Bardet-Biedl syndrome 4) This gene is a member of the Bardet-Biedl syndrome (BBS) gene family. Bardet-Biedl syndrome is an autosomal recessive disorder characterized by severe pigmentary retinopathy, obesity, polydactyly, renal malformation and cognitive disability. The proteins encoded by BBS gene family members are structurally diverse. The similar phenotypes exhibited by mutations in BBS gene family members are likely due to the protein's shared roles in cilia formation and function. Many BBS proteins localize to the basal bodies, ciliary axonemes, and pericentriolar regions of cells. BBS proteins may also be involved in intracellular trafficking via microtubule-related transport. The protein encoded by this gene has sequence similarity to O-linked N-acetylglucosamine (O-GlcNAc) transferases in plants and archaebacteria and in human forms a multi-protein "BBSome" complex with seven other BBS proteins. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Mar 2016]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BP6: Variant 15-72737433-T-C is Benign according to our data. Variant chr15-72737433-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 21732.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.116 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BBS4	NM_033028.5	c.1451-45T>C		intron_variant		ENST00000268057.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BBS4	ENST00000268057.9	c.1451-45T>C		intron_variant		1	NM_033028.5	P1

Frequencies

GnomAD3 genomes AF: 0.0849 AC: 12916 AN: 152142 Hom.: 668 Cov.: 32

Gnomad AFR AF: 0.0539

Gnomad AMI AF: 0.112

Gnomad AMR AF: 0.0611

Gnomad ASJ AF: 0.109

Gnomad EAS AF: 0.000577

Gnomad SAS AF: 0.0820

Gnomad FIN AF: 0.0603

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.118

Gnomad OTH AF: 0.0861

GnomAD3 exomes AF: 0.0813 AC: 16024 AN: 196986 Hom.: 741 AF XY: 0.0842 AC XY: 8815 AN XY: 104696

Gnomad AFR exome AF: 0.0505

Gnomad AMR exome AF: 0.0488

Gnomad ASJ exome AF: 0.105

Gnomad EAS exome AF: 0.000258

Gnomad SAS exome AF: 0.0846

Gnomad FIN exome AF: 0.0547

Gnomad NFE exome AF: 0.115

Gnomad OTH exome AF: 0.0815

GnomAD4 exome AF: 0.113 AC: 152567 AN: 1349256 Hom.: 9425 Cov.: 20 AF XY: 0.112 AC XY: 75334 AN XY: 671982

Gnomad4 AFR exome AF: 0.0533

Gnomad4 AMR exome AF: 0.0506

Gnomad4 ASJ exome AF: 0.106

Gnomad4 EAS exome AF: 0.000157

Gnomad4 SAS exome AF: 0.0897

Gnomad4 FIN exome AF: 0.0549

Gnomad4 NFE exome AF: 0.127

Gnomad4 OTH exome AF: 0.107

GnomAD4 genome AF: 0.0849 AC: 12924 AN: 152260 Hom.: 668 Cov.: 32 AF XY: 0.0810 AC XY: 6027 AN XY: 74452

Gnomad4 AFR AF: 0.0541

Gnomad4 AMR AF: 0.0610

Gnomad4 ASJ AF: 0.109

Gnomad4 EAS AF: 0.000579

Gnomad4 SAS AF: 0.0810

Gnomad4 FIN AF: 0.0603

Gnomad4 NFE AF: 0.118

Gnomad4 OTH AF: 0.0852

Alfa AF: 0.0977 Hom.: 126

Bravo AF: 0.0830

Asia WGS AF: 0.0360 AC: 124 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

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- -

Bardet-Biedl syndrome Benign:1

Benign, no assertion criteria provided

curation

GeneReviews

Oct 13, 2009

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
Cadd	Benign	14
Dann	Benign	0.87

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: rs75847960; hg19: chr15-73029774;