rs1287191197

Variant names:

• chr15-43197459-C-A
• rs1287191197
• NM_001114134.2:c.1919G>T

Your query was ambiguous. Multiple possible variants found:

• chr15-43197459-C-A
• chr15-43197459-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001114134.2(EPB42):​c.1919G>T​(p.Arg640Leu) 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. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: EPB42 NM_001114134.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.645

Genes affected

EPB42 (HGNC:3381): (erythrocyte membrane protein band 4.2) Erythrocyte membrane protein band 4.2 is an ATP-binding protein which may regulate the association of protein 3 with ankyrin. It probably has a role in erythrocyte shape and mechanical property regulation. Mutations in the EPB42 gene are associated with recessive spherocytic elliptocytosis and recessively transmitted hereditary hemolytic anemia. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ENSG00000285117 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11972743).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EPB42	NM_001114134.2	c.1919G>T	p.Arg640Leu	missense_variant	Exon 13 of 13	ENST00000441366.7	NP_001107606.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EPB42	ENST00000441366.7	c.1919G>T	p.Arg640Leu	missense_variant	Exon 13 of 13	1	NM_001114134.2	ENSP00000396616.2
ENSG00000285117	ENST00000563128.5	n.447+4385G>T		intron_variant	Intron 3 of 3	3		ENSP00000520455.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	2.9
DANN	Benign	0.93
DEOGEN2	Benign	0.25	.;.;.;T;.
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.22	N
LIST_S2	Benign	0.48	.;T;T;T;T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.12	T;T;T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.0	.;.;.;N;.
PrimateAI	Benign	0.20	T
PROVEAN	Benign	-1.6	.;.;N;N;.
REVEL	Benign	0.034
Sift	Benign	0.19	.;.;T;D;.
Sift4G	Benign	0.23	.;.;T;T;T
Polyphen		0.0070	B;B;B;B;.
Vest4		0.20, 0.19, 0.21
MutPred		0.59		.;.;.;Loss of catalytic residue at R640 (P = 0.0169);.;
MVP		0.13
ClinPred		0.095	T
GERP RS		-3.0
Varity_R		0.091
gMVP		0.49

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1287191197; hg19: chr15-43489657;