Variant 5-112165095-G-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_022140.5(EPB41L4A):c.1956C>G(p.Ser652Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000558 in 1,580,756 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.00044 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00057 ( 0 hom. )

Consequence

EPB41L4A
NM_022140.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: 4.69

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EPB41L4A	NM_022140.5 linkuse as main transcript	c.1956C>G	p.Ser652Arg	missense_variant	23/23	ENST00000261486.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
EPB41L4A	ENST00000261486.6 linkuse as main transcript	c.1956C>G	p.Ser652Arg	missense_variant	23/23	1	NM_022140.5	P1
EPB41L4A	ENST00000509342.6 linkuse as main transcript	n.404C>G		non_coding_transcript_exon_variant	6/6	5
EPB41L4A	ENST00000507810.5 linkuse as main transcript	n.952+3644C>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes

AF:

0.000437

AC:

AN:

123500

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000256

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000359

Gnomad ASJ

AF:

0.000962

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000628

Gnomad OTH

AF:

0.000630

GnomAD3 exomes

AF:

0.000509

AC:

105

AN:

206122

Hom.:

AF XY:

0.000604

AC XY:

AN XY:

112518

show subpopulations

Gnomad AFR exome

AF:

0.0000839

Gnomad AMR exome

AF:

0.000673

Gnomad ASJ exome

AF:

0.000665

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000565

Gnomad NFE exome

AF:

0.000812

Gnomad OTH exome

AF:

0.000194

GnomAD4 exome

AF:

0.000568

AC:

828

AN:

1457154

Hom.:

Cov.:

AF XY:

0.000560

AC XY:

406

AN XY:

725198

show subpopulations

Gnomad4 AFR exome

AF:

0.000120

Gnomad4 AMR exome

AF:

0.000515

Gnomad4 ASJ exome

AF:

0.00142

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.0000375

Gnomad4 NFE exome

AF:

0.000645

Gnomad4 OTH exome

AF:

0.000714

GnomAD4 genome

AF:

0.000437

AC:

AN:

123602

Hom.:

Cov.:

AF XY:

0.000305

AC XY:

AN XY:

58996

show subpopulations

Gnomad4 AFR

AF:

0.000255

Gnomad4 AMR

AF:

0.000358

Gnomad4 ASJ

AF:

0.000962

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000628

Gnomad4 OTH

AF:

0.000621

Alfa

AF:

0.000507

Hom.:

Bravo

AF:

0.000340

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000615

AC:

ExAC

AF:

0.000431

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 15, 2022

The c.1956C>G (p.S652R) alteration is located in exon 23 (coding exon 23) of the EPB41L4A gene. This alteration results from a C to G substitution at nucleotide position 1956, causing the serine (S) at amino acid position 652 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Sep 01, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.38

BayesDel_addAF

Uncertain

0.058

BayesDel_noAF

Pathogenic

0.23

Cadd

Benign

Dann

Uncertain

1.0

DEOGEN2

Benign

0.010

T;T

Eigen

Uncertain

0.22

Eigen_PC

Uncertain

0.36

FATHMM_MKL

Uncertain

0.91

LIST_S2

Uncertain

0.87

D;.

M_CAP

Benign

0.035

MetaRNN

Benign

0.078

T;T

MetaSVM

Uncertain

-0.15

MutationAssessor

Benign

0.97

L;L

MutationTaster

Benign

0.99

PrimateAI

Uncertain

0.54

Sift4G

Uncertain

0.052

T;T

Polyphen

0.61

P;P

Vest4

0.51

MutPred

0.086

Gain of MoRF binding (P = 0.0166);Gain of MoRF binding (P = 0.0166);

MVP

0.88

MPC

0.16

ClinPred

0.033

GERP RS

5.3

Varity_R

0.37

gMVP

0.49

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.23

Details are displayed if max score is > 0.2

DS_AL_spliceai

0.23

Position offset: 23

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