Variant chr9-109176554-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_019114.5(EPB41L4B):c.2630C>T(p.Ala877Val) variant causes a missense change. The variant allele was found at a frequency of 0.000725 in 1,605,702 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00080 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00072 ( 5 hom. )

Consequence

EPB41L4B
NM_019114.5 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: 4.00

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 Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0120204985).

BP6

Variant 9-109176554-G-A is Benign according to our data. Variant chr9-109176554-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 2353008.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=1}.

BS2

High Homozygotes in GnomAdExome4 at 5 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EPB41L4B	NM_019114.5 linkuse as main transcript	c.2630C>T	p.Ala877Val	missense_variant	25/26	ENST00000374566.8	NP_061987.3	Q9H329-1Q59GC2Q9NSG9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EPB41L4B	ENST00000374566.8 linkuse as main transcript	c.2630C>T	p.Ala877Val	missense_variant	25/26	1	NM_019114.5	ENSP00000363694.3		Q9H329-1

Frequencies

GnomAD3 genomes

AF:

0.000802

AC:

122

AN:

152166

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000265

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00236

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.000830

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000985

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.000817

AC:

199

AN:

243644

Hom.:

AF XY:

0.000998

AC XY:

132

AN XY:

132298

show subpopulations

Gnomad AFR exome

AF:

0.0000651

Gnomad AMR exome

AF:

0.000868

Gnomad ASJ exome

AF:

0.000618

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00149

Gnomad FIN exome

AF:

0.0000467

Gnomad NFE exome

AF:

0.00100

Gnomad OTH exome

AF:

0.00119

GnomAD4 exome

AF:

0.000717

AC:

1042

AN:

1453418

Hom.:

Cov.:

AF XY:

0.000738

AC XY:

533

AN XY:

722188

show subpopulations

Gnomad4 AFR exome

AF:

0.0000905

Gnomad4 AMR exome

AF:

0.000956

Gnomad4 ASJ exome

AF:

0.000387

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00152

Gnomad4 FIN exome

AF:

0.0000375

Gnomad4 NFE exome

AF:

0.000721

Gnomad4 OTH exome

AF:

0.000750

GnomAD4 genome

AF:

0.000801

AC:

122

AN:

152284

Hom.:

Cov.:

AF XY:

0.000739

AC XY:

AN XY:

74446

show subpopulations

Gnomad4 AFR

AF:

0.000265

Gnomad4 AMR

AF:

0.00235

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.000830

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000985

Gnomad4 OTH

AF:

0.000474

Alfa

AF:

0.00102

Hom.:

Bravo

AF:

0.000846

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00109

AC:

ExAC

AF:

0.000786

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00153

EpiControl

AF:

0.00155

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 20, 2021

The c.2630C>T (p.A877V) alteration is located in exon 25 (coding exon 25) of the EPB41L4B gene. This alteration results from a C to T substitution at nucleotide position 2630, causing the alanine (A) at amino acid position 877 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Nov 01, 2024

EPB41L4B: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.35

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.010

Eigen

Benign

-0.13

Eigen_PC

Benign

0.087

FATHMM_MKL

Uncertain

0.81

LIST_S2

Benign

0.79

M_CAP

Benign

0.030

MetaRNN

Benign

0.012

MetaSVM

Benign

-0.60

MutationAssessor

Benign

0.0

PrimateAI

Benign

0.37

PROVEAN

Benign

-0.39

REVEL

Benign

0.20

Sift

Benign

0.14

Sift4G

Benign

0.25

Polyphen

0.10

Vest4

0.17

MVP

0.40

MPC

0.25

ClinPred

0.041

GERP RS

4.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.082

gMVP

0.25

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