rs11231741

Positions:

• chr11-64279413-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+4769G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.218 in 152,164 control chromosomes in the GnomAD database, including 4,650 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 0.22 (4650 hom., cov: 31)
• Consequence: BAD NM_032989.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.578

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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.313 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BAD	NM_032989.3	c.187+4769G>A		intron_variant		ENST00000309032.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BAD	ENST00000309032.8	c.187+4769G>A		intron_variant		1	NM_032989.3	P1

Frequencies

GnomAD3 genomes AF: 0.219 AC: 33244 AN: 152046 Hom.: 4652 Cov.: 31

Gnomad AFR AF: 0.0575

Gnomad AMI AF: 0.368

Gnomad AMR AF: 0.180

Gnomad ASJ AF: 0.275

Gnomad EAS AF: 0.0905

Gnomad SAS AF: 0.297

Gnomad FIN AF: 0.262

Gnomad MID AF: 0.278

Gnomad NFE AF: 0.317

Gnomad OTH AF: 0.244

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

GnomAD4 genome AF: 0.218 AC: 33231 AN: 152164 Hom.: 4650 Cov.: 31 AF XY: 0.218 AC XY: 16183 AN XY: 74402

Gnomad4 AFR AF: 0.0574

Gnomad4 AMR AF: 0.180

Gnomad4 ASJ AF: 0.275

Gnomad4 EAS AF: 0.0905

Gnomad4 SAS AF: 0.297

Gnomad4 FIN AF: 0.262

Gnomad4 NFE AF: 0.317

Gnomad4 OTH AF: 0.241

Alfa AF: 0.297 Hom.: 11927

Bravo AF: 0.204

Asia WGS AF: 0.167 AC: 582 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.5
DANN	Benign	0.34

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: rs11231741; hg19: chr11-64046885;