Variant chr20-36198013-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2PP2BP4

The ENST00000338074.7(EPB41L1):c.1640C>A(p.Pro547His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,446 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P547R) has been classified as Benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

EPB41L1
ENST00000338074.7 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.43

Variant links:

Genes affected

EPB41L1 (HGNC:3378): (erythrocyte membrane protein band 4.1 like 1) Erythrocyte membrane protein band 4.1 (EPB41) is a multifunctional protein that mediates interactions between the erythrocyte cytoskeleton and the overlying plasma membrane. The encoded protein binds and stabilizes D2 and D3 dopamine receptors at the neuronal plasma membrane. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2015]

EPB41L1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP2

Missense variant in gene, where missense usually causes diseases (based on misZ statistic), EPB41L1. . Gene score misZ 1.9386 (greater than the threshold 3.09). Trascript score misZ 4.2392 (greater than threshold 3.09). GenCC has associacion of gene with intellectual disability, autosomal dominant 40, autosomal dominant non-syndromic intellectual disability, complex neurodevelopmental disorder.

BP4

Computational evidence support a benign effect (MetaRNN=0.37107116).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EPB41L1	NM_012156.2 linkuse as main transcript	c.1640C>A	p.Pro547His	missense_variant	14/22	ENST00000338074.7	NP_036288.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EPB41L1	ENST00000338074.7 linkuse as main transcript	c.1640C>A	p.Pro547His	missense_variant	14/22	1	NM_012156.2	ENSP00000337168	P5	Q9H4G0-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000402

AC:

AN:

248490

Hom.:

AF XY:

0.00

AC XY:

AN XY:

134966

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000546

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461446

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727022

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.23

BayesDel_addAF

Uncertain

0.14

BayesDel_noAF

Uncertain

-0.040

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.53

.;.;.;.;.;D;.;T

Eigen

Uncertain

0.20

Eigen_PC

Uncertain

0.26

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.95

.;D;D;D;D;D;.;D

M_CAP

Benign

0.049

MetaRNN

Benign

0.37

T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.85

MutationAssessor

Benign

0.69

.;.;.;.;.;N;.;.

MutationTaster

Benign

1.0

D;D;D;D;D;D;D

PrimateAI

Uncertain

0.67

PROVEAN

Uncertain

-2.4

N;D;N;.;.;D;D;N

REVEL

Uncertain

0.42

Sift

Uncertain

0.0010

D;D;D;.;.;D;D;D

Sift4G

Uncertain

0.017

D;D;D;D;T;D;D;T

Polyphen

0.047

B;D;B;.;D;D;.;.

Vest4

0.46

MutPred

0.24

.;.;.;Gain of loop (P = 0.0013);.;Gain of loop (P = 0.0013);Gain of loop (P = 0.0013);.;

MVP

0.64

MPC

0.43

ClinPred

0.89

GERP RS

5.2

Varity_R

0.42

gMVP

0.35

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