20-37525602-T-C

Variant names:

• chr20-37525602-T-C
• rs6090836
• NM_006698.4:c.-177+2191A>G

Variant summary

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

The NM_006698.4(BLCAP):​c.-177+2191A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.811 in 152,222 control chromosomes in the GnomAD database, including 50,465 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 0.81 (50465 hom., cov: 33)
• Consequence: BLCAP NM_006698.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00600
• Publications: 9 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.97 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BLCAP	NM_006698.4	MANE Select	c.-177+2191A>G		intron	N/A	NP_006689.1
	BLCAP	NM_001167820.2		c.-310+2191A>G		intron	N/A	NP_001161292.1
	BLCAP	NM_001167821.2		c.-177+2029A>G		intron	N/A	NP_001161293.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BLCAP	ENST00000373537.7	TSL:1 MANE Select	c.-177+2191A>G		intron	N/A	ENSP00000362637.2
	BLCAP	ENST00000397137.5	TSL:1	c.-177+2029A>G		intron	N/A	ENSP00000380326.1
	BLCAP	ENST00000397135.1	TSL:4	c.-177+1972A>G		intron	N/A	ENSP00000380324.1

Frequencies

GnomAD3 genomes AF: 0.811 AC: 123325 AN: 152104 Hom.: 50409 Cov.: 33

Gnomad AFR AF: 0.869

Gnomad AMI AF: 0.643

Gnomad AMR AF: 0.802

Gnomad ASJ AF: 0.595

Gnomad EAS AF: 0.993

Gnomad SAS AF: 0.810

Gnomad FIN AF: 0.904

Gnomad MID AF: 0.611

Gnomad NFE AF: 0.766

Gnomad OTH AF: 0.735

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

GnomAD4 genome AF: 0.811 AC: 123437 AN: 152222 Hom.: 50465 Cov.: 33 AF XY: 0.816 AC XY: 60746 AN XY: 74410

African (AFR) AF: 0.868 AC: 36074 AN: 41538

American (AMR) AF: 0.802 AC: 12268 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.595 AC: 2064 AN: 3470

East Asian (EAS) AF: 0.993 AC: 5148 AN: 5184

South Asian (SAS) AF: 0.810 AC: 3908 AN: 4826

European-Finnish (FIN) AF: 0.904 AC: 9586 AN: 10604

Middle Eastern (MID) AF: 0.605 AC: 178 AN: 294

European-Non Finnish (NFE) AF: 0.766 AC: 52068 AN: 67990

Other (OTH) AF: 0.737 AC: 1559 AN: 2114

Alfa AF: 0.766 Hom.: 23334

Bravo AF: 0.805

Asia WGS AF: 0.911 AC: 3164 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	7.1
DANN	Benign	0.88
PhyloP100		-0.0060
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: rs6090836; hg19: chr20-36154004;