rs477895

Positions:

• chr11-64281440-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_032989.3(BAD):​c.187+2742G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.74 in 152,156 control chromosomes in the GnomAD database, including 43,447 homozygotes. 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: 𝑓 0.74 (43447 hom., cov: 33)
• Consequence: BAD NM_032989.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.417

Genes affected

BAD (HGNC:936): (BCL2 associated agonist of cell death) The protein encoded by this gene is a member of the BCL-2 family. BCL-2 family members are known to be regulators of programmed cell death. This protein positively regulates cell apoptosis by forming heterodimers with BCL-xL (B-cell lymphoma-extra large) and BCL-2, and reversing their death repressor activity. Proapoptotic activity of this protein is regulated through its phosphorylation. Protein kinases AKT and MAP kinase, as well as protein phosphatase calcineurin were found to be involved in the regulation of this protein. Alternative splicing of this gene results in two transcript variants which encode the same isoform. [provided by RefSeq, Dec 2019]

GPR137 (HGNC:24300): (G protein-coupled receptor 137) Predicted to be involved in several processes, including negative regulation of bone resorption; negative regulation of osteoclast differentiation; and positive regulation of TORC1 signaling. Located in lysosomal membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.833 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BAD	NM_032989.3	c.187+2742G>A		intron_variant		ENST00000309032.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BAD	ENST00000309032.8	c.187+2742G>A		intron_variant		1	NM_032989.3	P1

Frequencies

GnomAD3 genomes AF: 0.741 AC: 112585 AN: 152038 Hom.: 43431 Cov.: 33

Gnomad AFR AF: 0.502

Gnomad AMI AF: 0.894

Gnomad AMR AF: 0.810

Gnomad ASJ AF: 0.884

Gnomad EAS AF: 0.817

Gnomad SAS AF: 0.756

Gnomad FIN AF: 0.834

Gnomad MID AF: 0.826

Gnomad NFE AF: 0.838

Gnomad OTH AF: 0.751

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.740 AC: 112643 AN: 152156 Hom.: 43447 Cov.: 33 AF XY: 0.743 AC XY: 55264 AN XY: 74412

Gnomad4 AFR AF: 0.502

Gnomad4 AMR AF: 0.810

Gnomad4 ASJ AF: 0.884

Gnomad4 EAS AF: 0.818

Gnomad4 SAS AF: 0.757

Gnomad4 FIN AF: 0.834

Gnomad4 NFE AF: 0.838

Gnomad4 OTH AF: 0.746

Alfa AF: 0.813 Hom.: 38185

Bravo AF: 0.732

Asia WGS AF: 0.757 AC: 2634 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	9.3
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: rs477895; hg19: chr11-64048912;