Variant 5-112194587-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_022140.5(EPB41L4A):c.1483T>C(p.Tyr495His) variant causes a missense change. The variant allele was found at a frequency of 0.736 in 1,593,080 control chromosomes in the GnomAD database, including 436,642 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 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 0.78 ( 47390 hom., cov: 32)

Exomes 𝑓: 0.73 ( 389252 hom. )

Consequence

EPB41L4A
NM_022140.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.38

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:

ENSG00000251187 (HGNC:):

ENSG00000251187 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=5.7763503E-7).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.975 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EPB41L4A	NM_022140.5 link	c.1483T>C	p.Tyr495His	missense_variant	17/23	ENST00000261486.6	NP_071423.4	Q9HCS5Q8NEH8Q8N8X1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EPB41L4A	ENST00000261486.6 link	c.1483T>C	p.Tyr495His	missense_variant	17/23	1	NM_022140.5	ENSP00000261486.5		Q9HCS5

Frequencies

GnomAD3 genomes

AF:

0.784

AC:

119175

AN:

152054

Hom.:

47338

Cov.:

show subpopulations

Gnomad AFR

AF:

0.877

Gnomad AMI

AF:

0.584

Gnomad AMR

AF:

0.816

Gnomad ASJ

AF:

0.736

Gnomad EAS

AF:

0.997

Gnomad SAS

AF:

0.877

Gnomad FIN

AF:

0.751

Gnomad MID

AF:

0.807

Gnomad NFE

AF:

0.707

Gnomad OTH

AF:

0.790

GnomAD3 exomes

AF:

0.784

AC:

188472

AN:

240312

Hom.:

75133

AF XY:

0.780

AC XY:

101705

AN XY:

130402

show subpopulations

Gnomad AFR exome

AF:

0.881

Gnomad AMR exome

AF:

0.870

Gnomad ASJ exome

AF:

0.755

Gnomad EAS exome

AF:

0.999

Gnomad SAS exome

AF:

0.857

Gnomad FIN exome

AF:

0.742

Gnomad NFE exome

AF:

0.706

Gnomad OTH exome

AF:

0.762

GnomAD4 exome

AF:

0.731

AC:

1053659

AN:

1440908

Hom.:

389252

Cov.:

AF XY:

0.734

AC XY:

526586

AN XY:

717326

show subpopulations

Gnomad4 AFR exome

AF:

0.879

Gnomad4 AMR exome

AF:

0.863

Gnomad4 ASJ exome

AF:

0.755

Gnomad4 EAS exome

AF:

0.999

Gnomad4 SAS exome

AF:

0.854

Gnomad4 FIN exome

AF:

0.741

Gnomad4 NFE exome

AF:

0.700

Gnomad4 OTH exome

AF:

0.755

GnomAD4 genome

AF:

0.784

AC:

119287

AN:

152172

Hom.:

47390

Cov.:

AF XY:

0.790

AC XY:

58746

AN XY:

74394

show subpopulations

Gnomad4 AFR

AF:

0.877

Gnomad4 AMR

AF:

0.816

Gnomad4 ASJ

AF:

0.736

Gnomad4 EAS

AF:

0.997

Gnomad4 SAS

AF:

0.875

Gnomad4 FIN

AF:

0.751

Gnomad4 NFE

AF:

0.707

Gnomad4 OTH

AF:

0.793

Alfa

AF:

0.724

Hom.:

91122

Bravo

AF:

0.792

TwinsUK

AF:

0.719

AC:

2665

ALSPAC

AF:

0.689

AC:

2656

ESP6500AA

AF:

0.879

AC:

3185

ESP6500EA

AF:

0.713

AC:

5805

ExAC

AF:

0.785

AC:

94822

Asia WGS

AF:

0.933

AC:

3241

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.068

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.44

CADD

Benign

DANN

Benign

0.85

DEOGEN2

Benign

0.0045

T;T

Eigen

Benign

-0.77

Eigen_PC

Benign

-0.43

FATHMM_MKL

Benign

0.010

LIST_S2

Benign

0.052

T;.

MetaRNN

Benign

5.8e-7

T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

-1.9

N;N

PrimateAI

Uncertain

0.67

PROVEAN

Benign

2.3

.;N

REVEL

Uncertain

0.33

Sift

Benign

1.0

.;T

Sift4G

Benign

1.0

T;T

Polyphen

0.0

B;B

Vest4

0.23

MPC

0.049

ClinPred

0.0067

GERP RS

5.1

Varity_R

0.057

gMVP

0.39

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over