Variant 9-109255549-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_019114.5(EPB41L4B):c.1131A>C(p.Arg377Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000942 in 1,614,194 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 0.000079 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000096 ( 0 hom. )

Consequence

EPB41L4B
NM_019114.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.600

Variant links:

Genes affected

EPB41L4B (HGNC:19818): (erythrocyte membrane protein band 4.1 like 4B) Predicted to be a structural constituent of cytoskeleton. Involved in several processes, including positive regulation of cell adhesion; positive regulation of keratinocyte migration; and wound healing. Acts upstream of or within actomyosin structure organization. Located in apical part of cell; cytosol; and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

EPB41L4B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.16165003).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EPB41L4B	NM_019114.5 linkuse as main transcript	c.1131A>C	p.Arg377Ser	missense_variant	11/26	ENST00000374566.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EPB41L4B	ENST00000374566.8 linkuse as main transcript	c.1131A>C	p.Arg377Ser	missense_variant	11/26	1	NM_019114.5	P3	Q9H329-1
EPB41L4B	ENST00000374557.4 linkuse as main transcript	c.1131A>C	p.Arg377Ser	missense_variant	11/16	1		A1	Q9H329-2

Frequencies

GnomAD3 genomes

AF:

0.0000789

AC:

AN:

152186

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.000577

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.000960

GnomAD3 exomes

AF:

0.000216

AC:

AN:

249572

Hom.:

AF XY:

0.000229

AC XY:

AN XY:

135400

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000434

Gnomad ASJ exome

AF:

0.000496

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000196

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000247

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000958

AC:

140

AN:

1461890

Hom.:

Cov.:

AF XY:

0.000114

AC XY:

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000380

Gnomad4 ASJ exome

AF:

0.000230

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000301

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000710

Gnomad4 OTH exome

AF:

0.000166

GnomAD4 genome

AF:

0.0000788

AC:

AN:

152304

Hom.:

Cov.:

AF XY:

0.000107

AC XY:

AN XY:

74490

show subpopulations

Gnomad4 AFR

AF:

0.0000481

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.000577

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000882

Gnomad4 OTH

AF:

0.000950

Alfa

AF:

0.000175

Hom.:

Bravo

AF:

0.000110

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000241

AC:

ExAC

AF:

0.000141

AC:

EpiCase

AF:

0.000327

EpiControl

AF:

0.000296

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 16, 2022

The c.1131A>C (p.R377S) alteration is located in exon 11 (coding exon 11) of the EPB41L4B gene. This alteration results from a A to C substitution at nucleotide position 1131, causing the arginine (R) at amino acid position 377 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.64

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.14

Cadd

Benign

Dann

Uncertain

0.99

DEOGEN2

Benign

0.21

T;.

Eigen

Benign

-0.60

Eigen_PC

Benign

-0.64

FATHMM_MKL

Benign

0.74

LIST_S2

Benign

0.84

T;T

M_CAP

Benign

0.080

MetaRNN

Benign

0.16

T;T

MetaSVM

Benign

-0.70

MutationAssessor

Uncertain

2.2

M;M

MutationTaster

Benign

1.0

D;D

PrimateAI

Benign

0.45

PROVEAN

Pathogenic

-5.7

D;D

REVEL

Uncertain

0.35

Sift

Uncertain

0.0020

D;D

Sift4G

Pathogenic

0.0010

D;D

Polyphen

0.43

B;B

Vest4

0.49

MutPred

0.46

Loss of MoRF binding (P = 0.0398);Loss of MoRF binding (P = 0.0398);

MVP

0.71

MPC

0.88

ClinPred

0.14

GERP RS

-2.8

Varity_R

0.46

gMVP

0.53

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