chr20-36209753-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_012156.2(EPB41L1):c.1934G>A(p.Arg645Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000385 in 1,614,086 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00062 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00036 ( 1 hom. )

Consequence

EPB41L1
NM_012156.2 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 1.25

Publications

5 publications found

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 Gene-Disease associations (from GenCC):

autosomal dominant non-syndromic intellectual disability
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
complex neurodevelopmental disorder
Inheritance: AD Classification: LIMITED Submitted by: ClinGen
intellectual disability, autosomal dominant 11
Inheritance: AD Classification: LIMITED Submitted by: G2P

EPB41L1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0059729517).

BP6

Variant 20-36209753-G-A is Benign according to our data. Variant chr20-36209753-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 435069.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 94 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EPB41L1	NM_012156.2 link	c.1934G>A	p.Arg645Gln	missense_variant	Exon 15 of 22	ENST00000338074.7	NP_036288.2	Q9H4G0-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EPB41L1	ENST00000338074.7 link	c.1934G>A	p.Arg645Gln	missense_variant	Exon 15 of 22	1	NM_012156.2	ENSP00000337168.2		Q9H4G0-1

Frequencies

GnomAD3 genomes

AF:

0.000618

AC:

AN:

152142

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00275

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00597

Gnomad SAS

AF:

0.00104

Gnomad FIN

AF:

0.000565

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.000958

GnomAD2 exomes

AF:

0.00107

AC:

268

AN:

251256

AF XY:

0.000957

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.00240

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00745

Gnomad FIN exome

AF:

0.000739

Gnomad NFE exome

AF:

0.000114

Gnomad OTH exome

AF:

0.000326

GnomAD4 exome

AF:

0.000361

AC:

527

AN:

1461826

Hom.:

Cov.:

AF XY:

0.000352

AC XY:

256

AN XY:

727228

show subpopulations

African (AFR)

AF:

0.000209

AC:

AN:

33480

American (AMR)

AF:

0.00309

AC:

138

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00494

AC:

196

AN:

39698

South Asian (SAS)

AF:

0.000394

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.000562

AC:

AN:

53358

Middle Eastern (MID)

AF:

0.000173

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0000836

AC:

AN:

1112010

Other (OTH)

AF:

0.000464

AC:

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

101

134

168

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000617

AC:

AN:

152260

Hom.:

Cov.:

AF XY:

0.000658

AC XY:

AN XY:

74450

show subpopulations

African (AFR)

AF:

0.000144

AC:

AN:

41532

American (AMR)

AF:

0.00275

AC:

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00599

AC:

AN:

5178

South Asian (SAS)

AF:

0.00104

AC:

AN:

4816

European-Finnish (FIN)

AF:

0.000565

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

68024

Other (OTH)

AF:

0.000948

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000409

Hom.:

Bravo

AF:

0.000895

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000914

AC:

111

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.000164

EpiControl

AF:

0.00

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

not specified

Benign:1

Jan 29, 2017

Genetic Services Laboratory, University of Chicago

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

EPB41L1-related disorder

Benign:1

Feb 01, 2021

PreventionGenetics, part of Exact Sciences

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.079

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.17

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.079

.;.;.;.;T;.

Eigen

Benign

-0.21

Eigen_PC

Benign

-0.045

FATHMM_MKL

Uncertain

0.79

LIST_S2

Uncertain

0.92

.;D;D;D;D;.

M_CAP

Benign

0.024

MetaRNN

Benign

0.0060

T;T;T;T;T;T

MetaSVM

Benign

-0.75

MutationAssessor

Benign

0.20

.;.;.;.;N;.

PhyloP100

1.3

PrimateAI

Benign

0.38

PROVEAN

Benign

-0.47

N;N;N;.;N;N

REVEL

Benign

0.26

Sift

Benign

0.14

T;D;T;.;D;D

Sift4G

Benign

0.46

T;T;T;T;T;T

Polyphen

0.011

B;B;B;.;B;.

Vest4

0.12

MVP

0.82

MPC

0.27

ClinPred

0.016

GERP RS

3.9

Varity_R

0.090

gMVP

0.44

Mutation Taster

=91/9

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over