rs11231740

Positions:

• chr11-64279169-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+5013G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.343 in 151,940 control chromosomes in the GnomAD database, including 10,932 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 0.34 (10932 hom., cov: 31)
• Consequence: BAD NM_032989.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0970

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=-0.75).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.477 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BAD	NM_032989.3	c.187+5013G>A		intron_variant		ENST00000309032.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BAD	ENST00000309032.8	c.187+5013G>A		intron_variant		1	NM_032989.3	P1

Frequencies

GnomAD3 genomes AF: 0.343 AC: 52061 AN: 151820 Hom.: 10933 Cov.: 31

Gnomad AFR AF: 0.106

Gnomad AMI AF: 0.477

Gnomad AMR AF: 0.313

Gnomad ASJ AF: 0.381

Gnomad EAS AF: 0.216

Gnomad SAS AF: 0.377

Gnomad FIN AF: 0.432

Gnomad MID AF: 0.433

Gnomad NFE AF: 0.482

Gnomad OTH AF: 0.395

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

GnomAD4 genome AF: 0.343 AC: 52057 AN: 151940 Hom.: 10932 Cov.: 31 AF XY: 0.341 AC XY: 25364 AN XY: 74274

Gnomad4 AFR AF: 0.106

Gnomad4 AMR AF: 0.312

Gnomad4 ASJ AF: 0.381

Gnomad4 EAS AF: 0.216

Gnomad4 SAS AF: 0.376

Gnomad4 FIN AF: 0.432

Gnomad4 NFE AF: 0.482

Gnomad4 OTH AF: 0.397

Alfa AF: 0.448 Hom.: 15961

Bravo AF: 0.323

Asia WGS AF: 0.295 AC: 1023 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	2.9
DANN	Benign	0.83

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: rs11231740; hg19: chr11-64046641;