Variant 9-109192339-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_019114.5(EPB41L4B):c.2240G>A(p.Gly747Glu) variant causes a missense change. The variant allele was found at a frequency of 0.000398 in 1,611,960 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 0.00027 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00041 ( 0 hom. )

Consequence

EPB41L4B
NM_019114.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.74

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 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.28052473).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EPB41L4B	NM_019114.5 linkuse as main transcript	c.2240G>A	p.Gly747Glu	missense_variant	22/26	ENST00000374566.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EPB41L4B	ENST00000374566.8 linkuse as main transcript	c.2240G>A	p.Gly747Glu	missense_variant	22/26	1	NM_019114.5	P3	Q9H329-1

Frequencies

GnomAD3 genomes

AF:

0.000269

AC:

AN:

152168

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000965

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000847

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000412

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000384

AC:

AN:

247710

Hom.:

AF XY:

0.000387

AC XY:

AN XY:

134392

show subpopulations

Gnomad AFR exome

AF:

0.000259

Gnomad AMR exome

AF:

0.0000294

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000264

Gnomad FIN exome

AF:

0.000604

Gnomad NFE exome

AF:

0.000604

Gnomad OTH exome

AF:

0.000167

GnomAD4 exome

AF:

0.000412

AC:

601

AN:

1459792

Hom.:

Cov.:

AF XY:

0.000397

AC XY:

288

AN XY:

726106

show subpopulations

Gnomad4 AFR exome

AF:

0.0000899

Gnomad4 AMR exome

AF:

0.0000451

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000105

Gnomad4 FIN exome

AF:

0.000524

Gnomad4 NFE exome

AF:

0.000489

Gnomad4 OTH exome

AF:

0.000249

GnomAD4 genome

AF:

0.000269

AC:

AN:

152168

Hom.:

Cov.:

AF XY:

0.000336

AC XY:

AN XY:

74354

show subpopulations

Gnomad4 AFR

AF:

0.0000965

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000847

Gnomad4 NFE

AF:

0.000412

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000427

Hom.:

Bravo

AF:

0.000230

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.000800

AC:

ESP6500EA

AF:

0.000609

AC:

ExAC

AF:

0.000414

AC:

EpiCase

AF:

0.000546

EpiControl

AF:

0.000415

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

Aug 02, 2021

The c.2240G>A (p.G747E) alteration is located in exon 22 (coding exon 22) of the EPB41L4B gene. This alteration results from a G to A substitution at nucleotide position 2240, causing the glycine (G) at amino acid position 747 to be replaced by a glutamic acid (E). 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

Benign

0.12

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.18

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.012

Eigen

Uncertain

0.38

Eigen_PC

Uncertain

0.39

FATHMM_MKL

Uncertain

0.84

LIST_S2

Benign

0.75

M_CAP

Benign

0.062

MetaRNN

Benign

0.28

MetaSVM

Uncertain

0.13

MutationAssessor

Benign

0.97

MutationTaster

Benign

0.70

PrimateAI

Benign

0.41

PROVEAN

Benign

-1.4

REVEL

Uncertain

0.37

Sift

Uncertain

0.0040

Sift4G

Benign

0.21

Polyphen

0.95

Vest4

0.53

MVP

0.27

MPC

0.79

ClinPred

0.29

GERP RS

4.5

Varity_R

0.23

gMVP

0.19

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