Variant 5-112204429-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_022140.5(EPB41L4A):c.1322G>A(p.Arg441His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00107 in 1,613,770 control chromosomes in the GnomAD database, including 21 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0056 ( 11 hom., cov: 32)

Exomes 𝑓: 0.00059 ( 10 hom. )

Consequence

EPB41L4A
NM_022140.5 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.69

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:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0046990514).

BP6

Variant 5-112204429-C-T is Benign according to our data. Variant chr5-112204429-C-T is described in ClinVar as [Benign]. Clinvar id is 708907.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00564 (858/152088) while in subpopulation AFR AF= 0.0198 (823/41486). AF 95% confidence interval is 0.0187. There are 11 homozygotes in gnomad4. There are 413 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd at 11 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EPB41L4A	NM_022140.5 linkuse as main transcript	c.1322G>A	p.Arg441His	missense_variant	15/23	ENST00000261486.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EPB41L4A	ENST00000261486.6 linkuse as main transcript	c.1322G>A	p.Arg441His	missense_variant	15/23	1	NM_022140.5	P1
	ENST00000506875.1 linkuse as main transcript	n.138C>T		non_coding_transcript_exon_variant	3/4	5

Frequencies

GnomAD3 genomes

AF:

0.00564

AC:

857

AN:

151970

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0199

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00171

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00383

GnomAD3 exomes

AF:

0.00139

AC:

346

AN:

249580

Hom.:

AF XY:

0.00117

AC XY:

159

AN XY:

135406

show subpopulations

Gnomad AFR exome

AF:

0.0209

Gnomad AMR exome

AF:

0.000492

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000980

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000883

Gnomad OTH exome

AF:

0.000330

GnomAD4 exome

AF:

0.000589

AC:

861

AN:

1461682

Hom.:

Cov.:

AF XY:

0.000516

AC XY:

375

AN XY:

727156

show subpopulations

Gnomad4 AFR exome

AF:

0.0217

Gnomad4 AMR exome

AF:

0.000760

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000580

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000360

Gnomad4 OTH exome

AF:

0.00132

GnomAD4 genome

AF:

0.00564

AC:

858

AN:

152088

Hom.:

Cov.:

AF XY:

0.00555

AC XY:

413

AN XY:

74348

show subpopulations

Gnomad4 AFR

AF:

0.0198

Gnomad4 AMR

AF:

0.00170

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00379

Alfa

AF:

0.000935

Hom.:

Bravo

AF:

0.00654

ESP6500AA

AF:

0.0215

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00171

AC:

207

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.087

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.26

Cadd

Benign

Dann

Uncertain

1.0

DEOGEN2

Benign

0.0086

T;T

Eigen

Benign

-0.000074

Eigen_PC

Benign

0.099

FATHMM_MKL

Benign

0.75

LIST_S2

Uncertain

0.87

D;.

MetaRNN

Benign

0.0047

T;T

MetaSVM

Benign

-0.66

MutationAssessor

Benign

1.0

L;L

MutationTaster

Benign

0.98

PrimateAI

Benign

0.31

Sift4G

Benign

0.12

T;T

Polyphen

0.0020

B;B

Vest4

0.21

MVP

0.87

MPC

0.051

ClinPred

0.024

GERP RS

4.2

Varity_R

0.039

gMVP

0.40

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