rs515726214

Positions:

• chr15-43216262-A-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001114134.2(EPB42):​c.196+6T>A variant causes a splice donor region, intron 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. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: EPB42 NM_001114134.2 splice_donor_region, intron
• Scores: Splicing: ADA: 0.1186
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 2.34

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]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EPB42	NM_001114134.2	c.196+6T>A		splice_donor_region_variant, intron_variant		ENST00000441366.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EPB42	ENST00000441366.7	c.196+6T>A		splice_donor_region_variant, intron_variant		1	NM_001114134.2	P1
EPB42	ENST00000540029.5	c.196+6T>A		splice_donor_region_variant, intron_variant		2
EPB42	ENST00000648595.1	c.286+6T>A		splice_donor_region_variant, intron_variant

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

Hereditary spherocytosis type 5 Uncertain:1

Uncertain significance, no assertion criteria provided

literature only

ClinVar Staff, National Center for Biotechnology Information (NCBI)

Nov 10, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	12
DANN	Benign	0.84

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.12
dbscSNV1_RF	Benign	0.45
SpliceAI score (max)		0.59		Details are displayed if max score is > 0.2
DS_DL_spliceai		0.59		Position offset: 6

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs515726214; hg19: chr15-43508460;