rs45495503

Variant names:

• chr15-43206339-C-A
• rs45495503
• NM_001114134.2:c.1609G>T

Your query was ambiguous. Multiple possible variants found:

• chr15-43206339-C-A
• chr15-43206339-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.1609G>T​(p.Ala537Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,124 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 𝑓 0.0000066 (0 hom., cov: 32)
• Consequence: EPB42 NM_001114134.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.665

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=0.13277364).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EPB42	NM_001114134.2	c.1609G>T	p.Ala537Ser	missense_variant	Exon 10 of 13	ENST00000441366.7	NP_001107606.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EPB42	ENST00000441366.7	c.1609G>T	p.Ala537Ser	missense_variant	Exon 10 of 13	1	NM_001114134.2	ENSP00000396616.2
ENSG00000285117	ENST00000563128.5	n.143G>T		non_coding_transcript_exon_variant	Exon 1 of 4	3		ENSP00000520455.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152124 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 32

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152124 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74304

Gnomad4 AFR AF: 0.0000241

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.090
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	2.3
DANN	Benign	0.96
DEOGEN2	Benign	0.078	.;.;.;T;.
Eigen	Benign	-0.40
Eigen_PC	Benign	-0.35
FATHMM_MKL	Benign	0.55	D
LIST_S2	Benign	0.65	.;T;T;T;T
M_CAP	Benign	0.038	D
MetaRNN	Benign	0.13	T;T;T;T;T
MetaSVM	Benign	-0.77	T
MutationAssessor	Uncertain	2.2	.;.;.;M;.
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-0.61	.;.;N;N;.
REVEL	Benign	0.10
Sift	Benign	0.29	.;.;T;T;.
Sift4G	Benign	0.72	.;.;T;T;T
Polyphen		0.066	B;B;B;B;.
Vest4		0.11, 0.11, 0.14
MutPred		0.54		.;.;.;Gain of disorder (P = 0.0949);.;
MVP		0.77
ClinPred		0.16	T
GERP RS		3.7
Varity_R		0.045
gMVP		0.64

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: rs45495503; hg19: chr15-43498537;