20-37518999-T-C
Position:
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2
The NM_006698.4(BLCAP):āc.176A>Gā(p.Tyr59Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000644 in 1,614,086 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: š 0.000053 ( 0 hom., cov: 32)
Exomes š: 0.000066 ( 0 hom. )
Consequence
BLCAP
NM_006698.4 missense
NM_006698.4 missense
Scores
6
6
5
Clinical Significance
Conservation
PhyloP100: 7.81
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]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -4 ACMG points.
BS2
?
High AC in GnomAd4 at 8 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
BLCAP | NM_006698.4 | c.176A>G | p.Tyr59Cys | missense_variant | 2/2 | ENST00000373537.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
BLCAP | ENST00000373537.7 | c.176A>G | p.Tyr59Cys | missense_variant | 2/2 | 1 | NM_006698.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000526 AC: 8AN: 152192Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000795 AC: 20AN: 251486Hom.: 0 AF XY: 0.0000662 AC XY: 9AN XY: 135920
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GnomAD4 exome AF: 0.0000657 AC: 96AN: 1461894Hom.: 0 Cov.: 31 AF XY: 0.0000619 AC XY: 45AN XY: 727248
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GnomAD4 genome ? AF: 0.0000526 AC: 8AN: 152192Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3AN XY: 74350
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 06, 2023 | The c.176A>G (p.Y59C) alteration is located in exon 3 (coding exon 1) of the BLCAP gene. This alteration results from a A to G substitution at nucleotide position 176, causing the tyrosine (Y) at amino acid position 59 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Benign
T;T;T;T;T;T;T;T;.;.
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
M_CAP
Benign
D
MetaRNN
Uncertain
D;D;D;D;D;D;D;D;D;D
MetaSVM
Uncertain
T
MutationTaster
Benign
D;D;D;D;D;D
PrimateAI
Pathogenic
D
PROVEAN
Pathogenic
D;.;D;D;D;D;D;D;D;D
REVEL
Uncertain
Sift
Benign
D;.;D;D;D;D;D;D;D;D
Sift4G
Benign
T;.;T;T;T;T;T;.;.;T
Polyphen
D;D;D;D;D;D;D;D;.;.
Vest4
MVP
MPC
1.8
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at