chr15-72686190-C-A

Position:

chr15-72686190-C-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000395205.6(BBS4):c.-507C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0662 in 1,549,504 control chromosomes in the GnomAD database, including 3,973 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.047 ( 239 hom., cov: 32)

Exomes 𝑓: 0.068 ( 3734 hom. )

Consequence

BBS4
ENST00000395205.6 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -2.77

Variant links:

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]

BBS4 links:

HIGD2B (HGNC:26984): (HIG1 hypoxia inducible domain family member 2B) Predicted to be involved in mitochondrial respirasome assembly. Predicted to be integral component of membrane. Predicted to be active in mitochondrion. [provided by Alliance of Genome Resources, Apr 2022]

HIGD2B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 15-72686190-C-A is Benign according to our data. Variant chr15-72686190-C-A is described in ClinVar as [Benign]. Clinvar id is 262133.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-72686190-C-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0712 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HIGD2B	NM_001350932.3 linkuse as main transcript			upstream_gene_variant		ENST00000311755.6	NP_001337861.1
BBS4	NM_033028.5 linkuse as main transcript			upstream_gene_variant		ENST00000268057.9	NP_149017.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BBS4	ENST00000268057.9 linkuse as main transcript			upstream_gene_variant		1	NM_033028.5	ENSP00000268057	P1	Q96RK4-1
HIGD2B	ENST00000311755.6 linkuse as main transcript			upstream_gene_variant		1	NM_001350932.3	ENSP00000307951	P1

Frequencies

GnomAD3 genomes

AF:

0.0471

AC:

7164

AN:

152216

Hom.:

239

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0144

Gnomad AMI

AF:

0.0921

Gnomad AMR

AF:

0.0376

Gnomad ASJ

AF:

0.0199

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.0211

Gnomad FIN

AF:

0.0634

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.0729

Gnomad OTH

AF:

0.0488

GnomAD3 exomes

AF:

0.0458

AC:

7214

AN:

157460

Hom.:

249

AF XY:

0.0453

AC XY:

3786

AN XY:

83536

show subpopulations

Gnomad AFR exome

AF:

0.00973

Gnomad AMR exome

AF:

0.0352

Gnomad ASJ exome

AF:

0.0235

Gnomad EAS exome

AF:

0.0000851

Gnomad SAS exome

AF:

0.0215

Gnomad FIN exome

AF:

0.0606

Gnomad NFE exome

AF:

0.0725

Gnomad OTH exome

AF:

0.0465

GnomAD4 exome

AF:

0.0683

AC:

95471

AN:

1397170

Hom.:

3734

Cov.:

AF XY:

0.0672

AC XY:

46327

AN XY:

689498

show subpopulations

Gnomad4 AFR exome

AF:

0.00979

Gnomad4 AMR exome

AF:

0.0360

Gnomad4 ASJ exome

AF:

0.0215

Gnomad4 EAS exome

AF:

0.000111

Gnomad4 SAS exome

AF:

0.0217

Gnomad4 FIN exome

AF:

0.0584

Gnomad4 NFE exome

AF:

0.0794

Gnomad4 OTH exome

AF:

0.0542

GnomAD4 genome

AF:

0.0470

AC:

7163

AN:

152334

Hom.:

239

Cov.:

AF XY:

0.0453

AC XY:

3378

AN XY:

74500

show subpopulations

Gnomad4 AFR

AF:

0.0144

Gnomad4 AMR

AF:

0.0375

Gnomad4 ASJ

AF:

0.0199

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.0211

Gnomad4 FIN

AF:

0.0634

Gnomad4 NFE

AF:

0.0729

Gnomad4 OTH

AF:

0.0478

Alfa

AF:

0.0647

Hom.:

446

Bravo

AF:

0.0438

Asia WGS

AF:

0.00779

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

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

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Bardet-Biedl syndrome 4

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

0.030

DANN

Benign

0.86

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over