20-37518928-C-T

Position:

• chr20-37518928-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000373537.7(BLCAP):​c.247G>A​(p.Gly83Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: BLCAP ENST00000373537.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.32

Genes affected

BLCAP (HGNC:1055): (BLCAP apoptosis inducing factor) This gene encodes a protein that reduces cell growth by stimulating apoptosis. Alternative splicing and the use of alternative promoters result in multiple transcript variants encoding the same protein. This gene is imprinted in brain where different transcript variants are expressed from each parental allele. Transcript variants initiating from the upstream promoter are expressed preferentially from the maternal allele, while transcript variants initiating downstream of the interspersed NNAT gene (GeneID:4826) are expressed from the paternal allele. Transcripts at this locus may also undergo A to I editing, resulting in amino acid changes at three positions in the N-terminus of the protein. [provided by RefSeq, Nov 2015]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05686453).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BLCAP	NM_006698.4	c.247G>A	p.Gly83Ser	missense_variant	2/2	ENST00000373537.7	NP_006689.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BLCAP	ENST00000373537.7	c.247G>A	p.Gly83Ser	missense_variant	2/2	1	NM_006698.4	ENSP00000362637	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 28, 2024

The c.247G>A (p.G83S) alteration is located in exon 3 (coding exon 1) of the BLCAP gene. This alteration results from a G to A substitution at nucleotide position 247, causing the glycine (G) at amino acid position 83 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.058
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	17
DANN	Benign	0.88
DEOGEN2	Benign	0.047	T;T;T;T;T;T;T;T
Eigen	Benign	-0.64
Eigen_PC	Benign	-0.57
FATHMM_MKL	Benign	0.39	N
LIST_S2	Benign	0.83	.;.;.;T;.;.;.;.
M_CAP	Benign	0.0018	T
MetaRNN	Benign	0.057	T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.99	T
MutationTaster	Benign	1.0	N;N;N;N;N;N
PrimateAI	Benign	0.42	T
PROVEAN	Benign	0.050	N;.;N;N;N;N;N;N
REVEL	Benign	0.036
Sift	Benign	1.0	T;.;T;T;T;T;T;T
Sift4G	Benign	0.77	T;.;T;T;T;T;T;.
Polyphen		0.0	B;B;B;B;B;B;B;B
Vest4		0.030
MutPred		0.21		Gain of glycosylation at G83 (P = 0.0054);Gain of glycosylation at G83 (P = 0.0054);Gain of glycosylation at G83 (P = 0.0054);Gain of glycosylation at G83 (P = 0.0054);Gain of glycosylation at G83 (P = 0.0054);Gain of glycosylation at G83 (P = 0.0054);Gain of glycosylation at G83 (P = 0.0054);Gain of glycosylation at G83 (P = 0.0054);
MVP		0.048
MPC		0.61
ClinPred		0.14	T
GERP RS		1.8
Varity_R		0.030
gMVP		0.64

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: rs1292313868; hg19: chr20-36147330; COSMIC: COSV99029976; COSMIC: COSV99029976;