Variant chr15-72736727-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_033028.5(BBS4):c.1249-35G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0334 in 1,609,610 control chromosomes in the GnomAD database, including 1,040 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.026 ( 57 hom., cov: 32)

Exomes 𝑓: 0.034 ( 983 hom. )

Consequence

BBS4
NM_033028.5 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.215

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 15-72736727-G-C is Benign according to our data. Variant chr15-72736727-G-C is described in ClinVar as [Benign]. Clinvar id is 262137.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0258 (3922/152282) while in subpopulation NFE AF= 0.0361 (2456/68024). AF 95% confidence interval is 0.0349. There are 57 homozygotes in gnomad4. There are 1821 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 57 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BBS4	NM_033028.5 linkuse as main transcript	c.1249-35G>C		intron_variant		ENST00000268057.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BBS4	ENST00000268057.9 linkuse as main transcript	c.1249-35G>C		intron_variant		1	NM_033028.5	P1	Q96RK4-1

Frequencies

GnomAD3 genomes

AF:

0.0257

AC:

3912

AN:

152164

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00697

Gnomad AMI

AF:

0.0822

Gnomad AMR

AF:

0.0332

Gnomad ASJ

AF:

0.0380

Gnomad EAS

AF:

0.00231

Gnomad SAS

AF:

0.0174

Gnomad FIN

AF:

0.0277

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.0361

Gnomad OTH

AF:

0.0278

GnomAD3 exomes

AF:

0.0306

AC:

7643

AN:

249830

Hom.:

164

AF XY:

0.0309

AC XY:

4183

AN XY:

135208

show subpopulations

Gnomad AFR exome

AF:

0.00629

Gnomad AMR exome

AF:

0.0359

Gnomad ASJ exome

AF:

0.0411

Gnomad EAS exome

AF:

0.00181

Gnomad SAS exome

AF:

0.0172

Gnomad FIN exome

AF:

0.0299

Gnomad NFE exome

AF:

0.0396

Gnomad OTH exome

AF:

0.0382

GnomAD4 exome

AF:

0.0341

AC:

49766

AN:

1457328

Hom.:

983

Cov.:

AF XY:

0.0340

AC XY:

24624

AN XY:

725302

show subpopulations

Gnomad4 AFR exome

AF:

0.00665

Gnomad4 AMR exome

AF:

0.0359

Gnomad4 ASJ exome

AF:

0.0399

Gnomad4 EAS exome

AF:

0.00111

Gnomad4 SAS exome

AF:

0.0164

Gnomad4 FIN exome

AF:

0.0302

Gnomad4 NFE exome

AF:

0.0377

Gnomad4 OTH exome

AF:

0.0307

GnomAD4 genome

AF:

0.0258

AC:

3922

AN:

152282

Hom.:

Cov.:

AF XY:

0.0245

AC XY:

1821

AN XY:

74460

show subpopulations

Gnomad4 AFR

AF:

0.00705

Gnomad4 AMR

AF:

0.0332

Gnomad4 ASJ

AF:

0.0380

Gnomad4 EAS

AF:

0.00231

Gnomad4 SAS

AF:

0.0184

Gnomad4 FIN

AF:

0.0277

Gnomad4 NFE

AF:

0.0361

Gnomad4 OTH

AF:

0.0285

Alfa

AF:

0.0175

Hom.:

Bravo

AF:

0.0261

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

1.7

DANN

Benign

0.35

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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