20-37518928-C-T

Variant names:

• chr20-37518928-C-T
• rs1292313868
• NM_006698.4:c.247G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_006698.4(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. 15/20 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 NM_006698.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.32
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006698.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BLCAP	NM_006698.4	MANE Select	c.247G>A	p.Gly83Ser	missense	Exon 2 of 2	NP_006689.1	P62952
	BLCAP	NM_001167820.2		c.247G>A	p.Gly83Ser	missense	Exon 3 of 3	NP_001161292.1	P62952
	BLCAP	NM_001167821.2		c.247G>A	p.Gly83Ser	missense	Exon 2 of 2	NP_001161293.1	P62952

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BLCAP	ENST00000373537.7	TSL:1 MANE Select	c.247G>A	p.Gly83Ser	missense	Exon 2 of 2	ENSP00000362637.2	P62952
	BLCAP	ENST00000397137.5	TSL:1	c.247G>A	p.Gly83Ser	missense	Exon 2 of 2	ENSP00000380326.1	P62952
	BLCAP	ENST00000397131.1	TSL:3	c.247G>A	p.Gly83Ser	missense	Exon 2 of 2	ENSP00000380320.1	P62952

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
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
MetaSVM	Benign	-0.99	T
PhyloP100		2.3
PrimateAI	Benign	0.42	T
PROVEAN	Benign	0.050	N
REVEL	Benign	0.036
Sift	Benign	1.0	T
Sift4G	Benign	0.77	T
Polyphen		0.0	B
Vest4		0.030
MutPred		0.21		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
Mutation Taster		=98/2	polymorphism

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