20-37525602-T-C

Position:

• chr20-37525602-T-C

Variant summary

Our verdict is Benign. Variant got -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

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]

BLCAP (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BLCAP	NM_006698.4	c.-177+2191A>G		intron_variant		ENST00000373537.7	NP_006689.1
BLCAP	NM_001167820.2	c.-310+2191A>G		intron_variant			NP_001161292.1
BLCAP	NM_001167821.2	c.-177+2029A>G		intron_variant			NP_001161293.1
BLCAP	NM_001167822.3	c.-177+1972A>G		intron_variant			NP_001161294.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BLCAP	ENST00000373537.7	c.-177+2191A>G		intron_variant		1	NM_006698.4	ENSP00000362637.2

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

Gnomad4 AFR AF: 0.868

Gnomad4 AMR AF: 0.802

Gnomad4 ASJ AF: 0.595

Gnomad4 EAS AF: 0.993

Gnomad4 SAS AF: 0.810

Gnomad4 FIN AF: 0.904

Gnomad4 NFE AF: 0.766

Gnomad4 OTH AF: 0.737

Alfa AF: 0.767 Hom.: 21094

Bravo AF: 0.805

Asia WGS AF: 0.911 AC: 3164 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	7.1
DANN	Benign	0.88

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: rs6090836; hg19: chr20-36154004;