Genetic Variant EPB41L4A:p.Asn526Ile (chr5-112184061-T-A) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_022140.5(EPB41L4A):c.1577A>T(p.Asn526Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00776 in 1,612,560 control chromosomes in the GnomAD database, including 56 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0056 ( 3 hom., cov: 33)

Exomes 𝑓: 0.0080 ( 53 hom. )

Consequence

EPB41L4A
NM_022140.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.682

Variant links:

Genes affected

EPB41L4A (HGNC:13278): (erythrocyte membrane protein band 4.1 like 4A) The protein encoded by this gene is a member of the band 4.1 protein superfamily. Members of this superfamily are thought to play an important role in regulating interactions between the cytoskeleton and plasma membrane, and contain an amino terminal conserved domain that binds glycophorin C. This gene product is thought to be involved in the beta-catenin signaling pathway. [provided by RefSeq, Dec 2016]

EPB41L4A links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004305899).

BP6

Variant 5-112184061-T-A is Benign according to our data. Variant chr5-112184061-T-A is described in ClinVar as [Likely_benign]. Clinvar id is 3777792.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EPB41L4A	NM_022140.5 link	c.1577A>T	p.Asn526Ile	missense_variant	Exon 18 of 23	ENST00000261486.6	NP_071423.4	Q9HCS5Q8NEH8Q8N8X1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
EPB41L4A	ENST00000261486.6 link	c.1577A>T	p.Asn526Ile	missense_variant	Exon 18 of 23	1	NM_022140.5	ENSP00000261486.5	Q9HCS5
EPB41L4A	ENST00000507810.5 link	n.597A>T		non_coding_transcript_exon_variant	Exon 7 of 14	2
EPB41L4A	ENST00000515047.5 link	n.397A>T		non_coding_transcript_exon_variant	Exon 5 of 7	3

Frequencies

GnomAD3 genomes

AF:

0.00557

AC:

848

AN:

152140

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00169

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00321

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00145

Gnomad FIN

AF:

0.00877

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00897

Gnomad OTH

AF:

0.00669

GnomAD3 exomes

AF:

0.00552

AC:

1376

AN:

249464

Hom.:

AF XY:

0.00543

AC XY:

735

AN XY:

135376

show subpopulations

Gnomad AFR exome

AF:

0.000904

Gnomad AMR exome

AF:

0.00171

Gnomad ASJ exome

AF:

0.00248

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00160

Gnomad FIN exome

AF:

0.00858

Gnomad NFE exome

AF:

0.00891

Gnomad OTH exome

AF:

0.00594

GnomAD4 exome

AF:

0.00799

AC:

11664

AN:

1460302

Hom.:

Cov.:

AF XY:

0.00787

AC XY:

5720

AN XY:

726452

show subpopulations

Gnomad4 AFR exome

AF:

0.000867

Gnomad4 AMR exome

AF:

0.00195

Gnomad4 ASJ exome

AF:

0.00237

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00165

Gnomad4 FIN exome

AF:

0.00849

Gnomad4 NFE exome

AF:

0.00948

Gnomad4 OTH exome

AF:

0.00578

GnomAD4 genome

AF:

0.00558

AC:

849

AN:

152258

Hom.:

Cov.:

AF XY:

0.00543

AC XY:

404

AN XY:

74448

show subpopulations

Gnomad4 AFR

AF:

0.00168

Gnomad4 AMR

AF:

0.00320

Gnomad4 ASJ

AF:

0.00144

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00166

Gnomad4 FIN

AF:

0.00877

Gnomad4 NFE

AF:

0.00897

Gnomad4 OTH

AF:

0.00662

Alfa

AF:

0.00815

Hom.:

Bravo

AF:

0.00483

TwinsUK

AF:

0.00971

AC:

ALSPAC

AF:

0.0135

AC:

ESP6500AA

AF:

0.00187

AC:

ESP6500EA

AF:

0.00877

AC:

ExAC

AF:

0.00554

AC:

669

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.00807

EpiControl

AF:

0.00800

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Mar 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

EPB41L4A: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.071

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.32

CADD

Benign

DANN

Benign

0.94

DEOGEN2

Benign

0.011

T;T

Eigen

Benign

-0.56

Eigen_PC

Benign

-0.41

FATHMM_MKL

Benign

0.45

LIST_S2

Uncertain

0.91

D;.

MetaRNN

Benign

0.0043

T;T

MetaSVM

Benign

-0.87

MutationAssessor

Benign

1.1

L;L

PrimateAI

Benign

0.42

PROVEAN

Benign

-1.9

.;N

REVEL

Benign

0.18

Sift

Benign

0.26

.;T

Sift4G

Benign

0.22

T;T

Polyphen

0.047

B;B

Vest4

0.31

MVP

0.64

MPC

0.049

ClinPred

0.0082

GERP RS

0.66

Varity_R

0.098

gMVP

0.48

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