rs3826007

Variant names:

• chr15-79970875-C-T
• rs3826007
• NM_004049.4:c.245G>A

Variant summary

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

The NM_004049.4(BCL2A1):​c.245G>A​(p.Gly82Asp) variant causes a missense change. The variant allele was found at a frequency of 0.246 in 1,613,944 control chromosomes in the GnomAD database, including 51,251 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 0.20 (3590 hom., cov: 33)
  • Exomes 𝑓: 0.25 (47661 hom.)
• Consequence: BCL2A1 NM_004049.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.23
• Publications: 46 publications found

Genes affected

BCL2A1 (HGNC:991): (BCL2 related protein A1) This gene encodes a member of the BCL-2 protein family. The proteins of this family form hetero- or homodimers and act as anti- and pro-apoptotic regulators that are involved in a wide variety of cellular activities such as embryonic development, homeostasis and tumorigenesis. The protein encoded by this gene is able to reduce the release of pro-apoptotic cytochrome c from mitochondria and block caspase activation. This gene is a direct transcription target of NF-kappa B in response to inflammatory mediators, and is up-regulated by different extracellular signals, such as granulocyte-macrophage colony-stimulating factor (GM-CSF), CD40, phorbol ester and inflammatory cytokine TNF and IL-1, which suggests a cytoprotective function that is essential for lymphocyte activation as well as cell survival. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=0.0018863976).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.328 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BCL2A1	NM_004049.4	c.245G>A	p.Gly82Asp	missense_variant	Exon 1 of 2	ENST00000267953.4	NP_004040.1
BCL2A1	NM_001114735.2	c.245G>A	p.Gly82Asp	missense_variant	Exon 1 of 3		NP_001108207.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BCL2A1	ENST00000267953.4	c.245G>A	p.Gly82Asp	missense_variant	Exon 1 of 2	1	NM_004049.4	ENSP00000267953.3
BCL2A1	ENST00000335661.6	c.245G>A	p.Gly82Asp	missense_variant	Exon 1 of 3	1		ENSP00000335250.6
BCL2A1	ENST00000677151.1	c.245G>A	p.Gly82Asp	missense_variant	Exon 1 of 1			ENSP00000504466.1

Frequencies

GnomAD3 genomes AF: 0.203 AC: 30856 AN: 152140 Hom.: 3588 Cov.: 33

Gnomad AFR AF: 0.0907

Gnomad AMI AF: 0.415

Gnomad AMR AF: 0.183

Gnomad ASJ AF: 0.213

Gnomad EAS AF: 0.222

Gnomad SAS AF: 0.341

Gnomad FIN AF: 0.233

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.255

Gnomad OTH AF: 0.227

GnomAD2 exomes AF: 0.231 AC: 58082 AN: 251346 AF XY: 0.241

Gnomad AFR exome AF: 0.0874

Gnomad AMR exome AF: 0.138

Gnomad ASJ exome AF: 0.210

Gnomad EAS exome AF: 0.238

Gnomad FIN exome AF: 0.229

Gnomad NFE exome AF: 0.253

Gnomad OTH exome AF: 0.244

GnomAD4 exome AF: 0.251 AC: 366521 AN: 1461686 Hom.: 47661 Cov.: 34 AF XY: 0.254 AC XY: 184703 AN XY: 727146

African (AFR) AF: 0.0828 AC: 2773 AN: 33478

American (AMR) AF: 0.143 AC: 6401 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.216 AC: 5651 AN: 26136

East Asian (EAS) AF: 0.220 AC: 8753 AN: 39700

South Asian (SAS) AF: 0.333 AC: 28732 AN: 86246

European-Finnish (FIN) AF: 0.227 AC: 12140 AN: 53420

Middle Eastern (MID) AF: 0.279 AC: 1608 AN: 5768

European-Non Finnish (NFE) AF: 0.257 AC: 285358 AN: 1111824

Other (OTH) AF: 0.250 AC: 15105 AN: 60390

GnomAD4 genome AF: 0.203 AC: 30865 AN: 152258 Hom.: 3590 Cov.: 33 AF XY: 0.204 AC XY: 15204 AN XY: 74434

African (AFR) AF: 0.0906 AC: 3765 AN: 41562

American (AMR) AF: 0.183 AC: 2798 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.213 AC: 738 AN: 3472

East Asian (EAS) AF: 0.223 AC: 1157 AN: 5192

South Asian (SAS) AF: 0.341 AC: 1648 AN: 4828

European-Finnish (FIN) AF: 0.233 AC: 2469 AN: 10598

Middle Eastern (MID) AF: 0.238 AC: 70 AN: 294

European-Non Finnish (NFE) AF: 0.255 AC: 17363 AN: 67990

Other (OTH) AF: 0.227 AC: 480 AN: 2112

Alfa AF: 0.234 Hom.: 21666

Bravo AF: 0.192

TwinsUK AF: 0.256 AC: 951

ALSPAC AF: 0.254 AC: 977

ESP6500AA AF: 0.0921 AC: 406

ESP6500EA AF: 0.254 AC: 2186

ExAC AF: 0.234 AC: 28459

Asia WGS AF: 0.256 AC: 893 AN: 3478

EpiCase AF: 0.251

EpiControl AF: 0.253

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.16
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.36	T;.
Eigen	Uncertain	0.66
Eigen_PC	Uncertain	0.56
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.82	T;T
MetaRNN	Benign	0.0019	T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Pathogenic	3.1	M;M
PhyloP100		4.2
PrimateAI	Uncertain	0.69	T
PROVEAN	Pathogenic	-6.0	D;D
REVEL	Uncertain	0.37
Sift	Benign	0.036	D;D
Sift4G	Uncertain	0.0080	D;D
Polyphen		1.0	D;.
Vest4		0.31
MPC		1.6
ClinPred		0.029	T
GERP RS		5.6
PromoterAI		-0.013	Neutral
Varity_R		0.86
gMVP		0.92
Mutation Taster		=94/6	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: rs3826007; hg19: chr15-80263217; COSMIC: COSV51212886;