11-64279400-A-T

Variant names:

• chr11-64279400-A-T
• rs7952435
• NM_032989.3:c.187+4782T>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_032989.3(BAD):​c.187+4782T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0928 in 151,934 control chromosomes in the GnomAD database, including 1,853 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 0.093 (1853 hom., cov: 32)
• Consequence: BAD NM_032989.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.479
• Publications: 3 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.282 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BAD	NM_032989.3	c.187+4782T>A		intron_variant	Intron 2 of 3	ENST00000309032.8	NP_116784.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BAD	ENST00000309032.8	c.187+4782T>A		intron_variant	Intron 2 of 3	1	NM_032989.3	ENSP00000309103.3

Frequencies

GnomAD3 genomes AF: 0.0926 AC: 14064 AN: 151816 Hom.: 1842 Cov.: 32

Gnomad AFR AF: 0.286

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0405

Gnomad ASJ AF: 0.00980

Gnomad EAS AF: 0.0749

Gnomad SAS AF: 0.184

Gnomad FIN AF: 0.000284

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.00235

Gnomad OTH AF: 0.0714

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

GnomAD4 genome AF: 0.0928 AC: 14101 AN: 151934 Hom.: 1853 Cov.: 32 AF XY: 0.0931 AC XY: 6913 AN XY: 74260

African (AFR) AF: 0.287 AC: 11867 AN: 41382

American (AMR) AF: 0.0403 AC: 615 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.00980 AC: 34 AN: 3470

East Asian (EAS) AF: 0.0749 AC: 387 AN: 5168

South Asian (SAS) AF: 0.183 AC: 878 AN: 4796

European-Finnish (FIN) AF: 0.000284 AC: 3 AN: 10582

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.00235 AC: 160 AN: 67970

Other (OTH) AF: 0.0711 AC: 150 AN: 2110

Alfa AF: 0.0509 Hom.: 114

Bravo AF: 0.0989

Asia WGS AF: 0.131 AC: 457 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.9
DANN	Benign	0.66
PhyloP100		0.48
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7952435; hg19: chr11-64046872;