4-122732786-G-A

Variant names:

• chr4-122732786-G-A
• rs886059057
• NM_152618.3:c.-109G>A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_152618.3(BBS12):​c.-109G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: BBS12 NM_152618.3 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.42

Genes affected

BBS12 (HGNC:26648): (Bardet-Biedl syndrome 12) The protein encoded by this gene is part of a complex that is involved in membrane trafficking. The encoded protein is a molecular chaperone that aids in protein folding upon ATP hydrolysis. This protein also plays a role in adipocyte differentiation. Defects in this gene are a cause of Bardet-Biedl syndrome type 12. Two transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, May 2010]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BBS12	NM_152618.3	c.-109G>A		5_prime_UTR_variant	Exon 1 of 2	ENST00000314218.8	NP_689831.2
BBS12	NM_001178007.2	c.-297G>A		5_prime_UTR_variant	Exon 1 of 3		NP_001171478.1
BBS12	XM_011531680.3	c.-10-9097G>A		intron_variant	Intron 1 of 1		XP_011529982.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BBS12	ENST00000314218	c.-109G>A		5_prime_UTR_variant	Exon 1 of 2	1	NM_152618.3	ENSP00000319062.3
BBS12	ENST00000542236	c.-297G>A		5_prime_UTR_variant	Exon 1 of 3	2		ENSP00000438273.1
BBS12	ENST00000433287.1	c.-297G>A		upstream_gene_variant		2		ENSP00000398912.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.12
DANN	Benign	0.75

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: rs886059057; hg19: chr4-123653941;