dbSNP rs75508009: EPB41L4A:p.Asn526Ile (chr5-112184061-T-A) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_022140.5(EPB41L4A):c.1577A>T(p.Asn526Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00776 in 1,612,560 control chromosomes in the GnomAD database, including 56 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0056 ( 3 hom., cov: 33)

Exomes 𝑓: 0.0080 ( 53 hom. )

Consequence

EPB41L4A
NM_022140.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.682

Publications

5 publications found

Variant links:

Genes affected

EPB41L4A (HGNC:13278): (erythrocyte membrane protein band 4.1 like 4A) The protein encoded by this gene is a member of the band 4.1 protein superfamily. Members of this superfamily are thought to play an important role in regulating interactions between the cytoskeleton and plasma membrane, and contain an amino terminal conserved domain that binds glycophorin C. This gene product is thought to be involved in the beta-catenin signaling pathway. [provided by RefSeq, Dec 2016]

EPB41L4A links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004305899).

BP6

Variant 5-112184061-T-A is Benign according to our data. Variant chr5-112184061-T-A is described in ClinVar as Likely_benign. ClinVar VariationId is 3777792.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022140.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
EPB41L4A	NM_022140.5	MANE Select	c.1577A>T	p.Asn526Ile	missense	Exon 18 of 23	NP_071423.4
EPB41L4A	NM_001347887.2		c.1577A>T	p.Asn526Ile	missense	Exon 18 of 24	NP_001334816.1
EPB41L4A	NR_144931.2		n.1815A>T		non_coding_transcript_exon	Exon 18 of 23

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
EPB41L4A	ENST00000261486.6	TSL:1 MANE Select	c.1577A>T	p.Asn526Ile	missense	Exon 18 of 23	ENSP00000261486.5	Q9HCS5
EPB41L4A	ENST00000507810.5	TSL:2	n.597A>T		non_coding_transcript_exon	Exon 7 of 14
EPB41L4A	ENST00000515047.5	TSL:3	n.397A>T		non_coding_transcript_exon	Exon 5 of 7

Frequencies

GnomAD3 genomes

AF:

0.00557

AC:

848

AN:

152140

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00169

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00321

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00145

Gnomad FIN

AF:

0.00877

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00897

Gnomad OTH

AF:

0.00669

GnomAD2 exomes

AF:

0.00552

AC:

1376

AN:

249464

AF XY:

0.00543

show subpopulations

Gnomad AFR exome

AF:

0.000904

Gnomad AMR exome

AF:

0.00171

Gnomad ASJ exome

AF:

0.00248

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00858

Gnomad NFE exome

AF:

0.00891

Gnomad OTH exome

AF:

0.00594

GnomAD4 exome

AF:

0.00799

AC:

11664

AN:

1460302

Hom.:

Cov.:

AF XY:

0.00787

AC XY:

5720

AN XY:

726452

show subpopulations

African (AFR)

AF:

0.000867

AC:

AN:

33450

American (AMR)

AF:

0.00195

AC:

AN:

44632

Ashkenazi Jewish (ASJ)

AF:

0.00237

AC:

AN:

26110

East Asian (EAS)

AF:

0.00

AC:

AN:

39642

South Asian (SAS)

AF:

0.00165

AC:

142

AN:

86172

European-Finnish (FIN)

AF:

0.00849

AC:

453

AN:

53334

Middle Eastern (MID)

AF:

0.00156

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00948

AC:

10533

AN:

1110852

Other (OTH)

AF:

0.00578

AC:

349

AN:

60342

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.451

Heterozygous variant carriers

626

1252

1877

2503

3129

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

374

748

1122

1496

1870

<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:

0.00558

AC:

849

AN:

152258

Hom.:

Cov.:

AF XY:

0.00543

AC XY:

404

AN XY:

74448

show subpopulations

African (AFR)

AF:

0.00168

AC:

AN:

41556

American (AMR)

AF:

0.00320

AC:

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00144

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5178

South Asian (SAS)

AF:

0.00166

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.00877

AC:

AN:

10608

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00897

AC:

610

AN:

68008

Other (OTH)

AF:

0.00662

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

127

170

212

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.00815

Hom.:

Bravo

AF:

0.00483

TwinsUK

AF:

0.00971

AC:

ALSPAC

AF:

0.0135

AC:

ESP6500AA

AF:

0.00187

AC:

ESP6500EA

AF:

0.00877

AC:

ExAC

AF:

0.00554

AC:

669

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.00807

EpiControl

AF:

0.00800

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.071

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.32

CADD

Benign

(source)

DANN

Benign

0.94

DEOGEN2

Benign

0.011

Eigen

Benign

-0.56

Eigen_PC

Benign

-0.41

FATHMM_MKL

Benign

0.45

LIST_S2

Uncertain

0.91

MetaRNN

Benign

0.0043

MetaSVM

Benign

-0.87

MutationAssessor

Benign

1.1

PhyloP100

-0.68

PrimateAI

Benign

0.42

PROVEAN

Benign

-1.9

REVEL

Benign

0.18

Sift

Benign

0.26

Sift4G

Benign

0.22

Polyphen

0.047

Vest4

0.31

MVP

0.64

MPC

0.049

ClinPred

0.0082

GERP RS

0.66

Varity_R

0.098

gMVP

0.48

Mutation Taster

=99/1

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over