Variant rs199993775 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 1P and 10B. PP2BP4_StrongBP6_ModerateBS2

The NM_012156.2(EPB41L1):c.2332A>G(p.Thr778Ala) variant causes a missense change. The variant allele was found at a frequency of 0.000371 in 1,614,096 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00064 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00034 ( 1 hom. )

Consequence

EPB41L1
NM_012156.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.61

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:

LOC105372602 (HGNC:):

LOC105372602 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

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=0.013405979).

BP6

Variant 20-36218939-A-G is Benign according to our data. Variant chr20-36218939-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 210949.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 98 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EPB41L1	NM_012156.2 linkuse as main transcript	c.2332A>G	p.Thr778Ala	missense_variant	18/22	ENST00000338074.7	NP_036288.2
LOC105372602	XR_936695.2 linkuse as main transcript	n.313+786T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EPB41L1	ENST00000338074.7 linkuse as main transcript	c.2332A>G	p.Thr778Ala	missense_variant	18/22	1	NM_012156.2	ENSP00000337168	P5	Q9H4G0-1

Frequencies

GnomAD3 genomes

AF:

0.000644

AC:

AN:

152222

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.00395

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000823

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000661

AC:

166

AN:

251056

Hom.:

AF XY:

0.000626

AC XY:

AN XY:

135746

show subpopulations

Gnomad AFR exome

AF:

0.0000616

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00516

Gnomad NFE exome

AF:

0.000432

Gnomad OTH exome

AF:

0.000653

GnomAD4 exome

AF:

0.000343

AC:

501

AN:

1461874

Hom.:

Cov.:

AF XY:

0.000340

AC XY:

247

AN XY:

727238

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00453

Gnomad4 NFE exome

AF:

0.000215

Gnomad4 OTH exome

AF:

0.000281

GnomAD4 genome

AF:

0.000644

AC:

AN:

152222

Hom.:

Cov.:

AF XY:

0.000767

AC XY:

AN XY:

74362

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00395

Gnomad4 NFE

AF:

0.000823

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000337

Hom.:

Bravo

AF:

0.000212

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000585

AC:

EpiCase

AF:

0.000327

EpiControl

AF:

0.000119

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Dec 17, 2015

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.068

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.14

CADD

Uncertain

DANN

Benign

0.94

DEOGEN2

Benign

0.11

.;.;.;.;.;T;.;T

Eigen

Benign

-0.050

Eigen_PC

Benign

0.060

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.78

.;T;T;T;T;T;.;T

M_CAP

Benign

0.050

MetaRNN

Benign

0.013

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

MetaSVM

Uncertain

-0.054

MutationAssessor

Benign

1.1

.;.;.;.;.;L;.;.

MutationTaster

Benign

0.99

D;D;N;N;N;N;N

PrimateAI

Uncertain

0.66

PROVEAN

Benign

-1.6

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

REVEL

Uncertain

0.43

Sift

Benign

0.10

T;T;T;.;.;T;T;T

Sift4G

Benign

0.81

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

Polyphen

0.033

B;B;B;.;P;B;.;.

Vest4

0.50

MVP

0.84

MPC

0.23

ClinPred

0.039

GERP RS

4.3

Varity_R

0.083

gMVP

0.34

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