chr15-72686222-G-A

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP6

The NM_033028.5(BBS4):​c.-6G>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 0.00000213 in 1,410,200 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

BBS4
NM_033028.5 5_prime_UTR

Scores

2

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 1.19
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]
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.54).
BP6
Variant 15-72686222-G-A is Benign according to our data. Variant chr15-72686222-G-A is described in ClinVar as [Benign]. Clinvar id is 21733.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
BBS4NM_033028.5 linkuse as main transcriptc.-6G>A 5_prime_UTR_variant 1/16 ENST00000268057.9
HIGD2BNM_001350932.3 linkuse as main transcript upstream_gene_variant ENST00000311755.6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
BBS4ENST00000268057.9 linkuse as main transcriptc.-6G>A 5_prime_UTR_variant 1/161 NM_033028.5 P1Q96RK4-1
HIGD2BENST00000311755.6 linkuse as main transcript upstream_gene_variant 1 NM_001350932.3 P1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000213
AC:
3
AN:
1410200
Hom.:
0
Cov.:
31
AF XY:
0.00000287
AC XY:
2
AN XY:
696742
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000125
Gnomad4 FIN exome
AF:
0.0000204
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.0000171
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

Bardet-Biedl syndrome Benign:1
Benign, no assertion criteria providedcurationGeneReviewsOct 13, 2009- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.54
CADD
Benign
13
DANN
Benign
0.88

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.

Other links and lift over

dbSNP: rs367543011; hg19: chr15-72978563; API