rs147654123

Variant names:

Your query was ambiguous. Multiple possible variants found:

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.1451C>T(p.Pro484Leu) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0035 in 1,613,990 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/24 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0020 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0037 ( 10 hom. )

Consequence

EPB41L1
NM_012156.2 missense, splice_region

Scores

Splicing: ADA: 0.9398

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 2.05

Publications

3 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:

LOC124904892 (HGNC:):

LOC124904892 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=0.0068655014).

BP6

Variant 20-36195330-C-T is Benign according to our data. Variant chr20-36195330-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 210943.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 304 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012156.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
EPB41L1	NM_012156.2	MANE Select	c.1451C>T	p.Pro484Leu	missense splice_region	Exon 13 of 22	NP_036288.2	Q9H4G0-1
EPB41L1	NM_001433605.1		c.1451C>T	p.Pro484Leu	missense splice_region	Exon 13 of 23	NP_001420534.1
EPB41L1	NM_001258329.1		c.1451C>T	p.Pro484Leu	missense splice_region	Exon 14 of 23	NP_001245258.1	A0A0C4DH22

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
EPB41L1	ENST00000338074.7	TSL:1 MANE Select	c.1451C>T	p.Pro484Leu	missense splice_region	Exon 13 of 22	ENSP00000337168.2	Q9H4G0-1
EPB41L1	ENST00000373946.7	TSL:1	c.1451C>T	p.Pro484Leu	missense splice_region	Exon 14 of 23	ENSP00000363057.4	A0A0C4DH22
EPB41L1	ENST00000202028.9	TSL:1	c.1263+970C>T		intron	N/A	ENSP00000202028.5	Q9H4G0-2

Frequencies

GnomAD3 genomes

AF:

0.00199

AC:

303

AN:

152036

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00102

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000458

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00366

Gnomad OTH

AF:

0.000479

GnomAD2 exomes

AF:

0.00172

AC:

433

AN:

251384

AF XY:

0.00167

show subpopulations

Gnomad AFR exome

AF:

0.000923

Gnomad AMR exome

AF:

0.000549

Gnomad ASJ exome

AF:

0.00109

Gnomad EAS exome

AF:

0.0000544

Gnomad FIN exome

AF:

0.000463

Gnomad NFE exome

AF:

0.00321

Gnomad OTH exome

AF:

0.00196

GnomAD4 exome

AF:

0.00365

AC:

5337

AN:

1461836

Hom.:

Cov.:

AF XY:

0.00348

AC XY:

2534

AN XY:

727228

show subpopulations

African (AFR)

AF:

0.000657

AC:

AN:

33480

American (AMR)

AF:

0.000648

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00107

AC:

AN:

26136

East Asian (EAS)

AF:

0.0000504

AC:

AN:

39698

South Asian (SAS)

AF:

0.00

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.000449

AC:

AN:

53394

Middle Eastern (MID)

AF:

0.000173

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00452

AC:

5026

AN:

1111984

Other (OTH)

AF:

0.00339

AC:

205

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.458

Heterozygous variant carriers

286

573

859

1146

1432

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

202

404

606

808

1010

<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:

0.00200

AC:

304

AN:

152154

Hom.:

Cov.:

AF XY:

0.00167

AC XY:

124

AN XY:

74404

show subpopulations

African (AFR)

AF:

0.00104

AC:

AN:

41478

American (AMR)

AF:

0.000458

AC:

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.000576

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5162

South Asian (SAS)

AF:

0.00

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.000188

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00366

AC:

249

AN:

68002

Other (OTH)

AF:

0.000474

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

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:

0.00272

Hom.:

Bravo

AF:

0.00186

TwinsUK

AF:

0.00512

AC:

ALSPAC

AF:

0.00259

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00314

AC:

ExAC

AF:

0.00162

AC:

197

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00289

EpiControl

AF:

0.00326

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

EPB41L1-related disorder (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.082

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.30

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.083

Eigen

Benign

-0.14

Eigen_PC

Benign

0.056

FATHMM_MKL

Uncertain

0.84

LIST_S2

Benign

0.83

M_CAP

Benign

0.031

MetaRNN

Benign

0.0069

MetaSVM

Benign

-0.67

MutationAssessor

Benign

0.69

PhyloP100

2.0

PrimateAI

Uncertain

0.68

PROVEAN

Benign

-0.89

REVEL

Benign

0.18

Sift

Benign

0.17

Sift4G

Benign

0.36

Polyphen

0.015

Vest4

0.25

MVP

0.29

MPC

0.23

ClinPred

0.016

GERP RS

5.2

Varity_R

0.090

gMVP

0.28

Mutation Taster

=77/23

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.94

dbscSNV1_RF

Benign

0.66

SpliceAI score (max)

0.010

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over