rs77809780

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000119.3(EPB42):c.29C>T(p.Ser10Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00601 in 1,612,802 control chromosomes in the GnomAD database, including 353 homozygotes. In-silico tool predicts a benign outcome for this variant. 9/14 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.027 ( 177 hom., cov: 31)

Exomes 𝑓: 0.0039 ( 176 hom. )

Consequence

EPB42
NM_000119.3 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.865

Variant links:

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]

EPB42 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0026146472).

BP6

Variant 15-43220797-G-A is Benign according to our data. Variant chr15-43220797-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 255152.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-43220797-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0851 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EPB42	NM_001114134.2 link	c.10+19C>T		intron_variant	Intron 1 of 12	ENST00000441366.7	NP_001107606.1	P16452-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
EPB42	ENST00000441366.7 link	c.10+19C>T		intron_variant	Intron 1 of 12	1	NM_001114134.2	ENSP00000396616.2	P16452-1
EPB42	ENST00000648595.1 link	c.29C>T	p.Ser10Leu	missense_variant	Exon 1 of 13			ENSP00000497777.1	P16452-2
EPB42	ENST00000540029.5 link	c.10+19C>T		intron_variant	Intron 1 of 11	2		ENSP00000444699.1	F5H563

Frequencies

GnomAD3 genomes

AF:

0.0266

AC:

4050

AN:

152000

Hom.:

175

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0875

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0104

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.0340

Gnomad SAS

AF:

0.00353

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000426

Gnomad OTH

AF:

0.0215

GnomAD3 exomes

AF:

0.00971

AC:

2433

AN:

250496

Hom.:

AF XY:

0.00807

AC XY:

1094

AN XY:

135500

show subpopulations

Gnomad AFR exome

AF:

0.0843

Gnomad AMR exome

AF:

0.00341

Gnomad ASJ exome

AF:

0.00159

Gnomad EAS exome

AF:

0.0404

Gnomad SAS exome

AF:

0.00356

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000378

Gnomad OTH exome

AF:

0.00554

GnomAD4 exome

AF:

0.00385

AC:

5629

AN:

1460684

Hom.:

176

Cov.:

AF XY:

0.00355

AC XY:

2580

AN XY:

726734

show subpopulations

Gnomad4 AFR exome

AF:

0.0876

Gnomad4 AMR exome

AF:

0.00456

Gnomad4 ASJ exome

AF:

0.00222

Gnomad4 EAS exome

AF:

0.0269

Gnomad4 SAS exome

AF:

0.00347

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000305

Gnomad4 OTH exome

AF:

0.0115

GnomAD4 genome

AF:

0.0267

AC:

4058

AN:

152118

Hom.:

177

Cov.:

AF XY:

0.0254

AC XY:

1886

AN XY:

74350

show subpopulations

Gnomad4 AFR

AF:

0.0874

Gnomad4 AMR

AF:

0.0103

Gnomad4 ASJ

AF:

0.00115

Gnomad4 EAS

AF:

0.0341

Gnomad4 SAS

AF:

0.00353

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000426

Gnomad4 OTH

AF:

0.0218

Alfa

AF:

0.00655

Hom.:

Bravo

AF:

0.0308

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.0833

AC:

367

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.0111

AC:

1349

Asia WGS

AF:

0.0430

AC:

148

AN:

3478

EpiCase

AF:

0.000763

EpiControl

AF:

0.000652

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Hereditary spherocytosis type 5

Benign:2

Jun 11, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. -

not provided

Benign:2

Jan 21, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.44

CADD

Benign

5.6

DANN

Uncertain

1.0

Eigen

Benign

-0.86

Eigen_PC

Benign

-0.94

FATHMM_MKL

Benign

0.22

LIST_S2

Benign

0.47

.;T

MetaRNN

Benign

0.0026

T;T

MetaSVM

Benign

-0.88

PrimateAI

Benign

0.40

Polyphen

0.010

B;B

ClinPred

0.028

GERP RS

-1.0

gMVP

0.44

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over