Variant 1-42830524-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_001017922.2(ERMAP):c.76C>T(p.His26Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.26 in 1,612,082 control chromosomes in the GnomAD database, including 58,849 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.21 ( 4385 hom., cov: 31)

Exomes 𝑓: 0.27 ( 54464 hom. )

Consequence

ERMAP
NM_001017922.2 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.177

Variant links:

Genes affected

ERMAP (HGNC:15743): (erythroblast membrane associated protein (Scianna blood group)) The protein encoded by this gene is a cell surface transmembrane protein that may act as an erythroid cell receptor, possibly as a mediator of cell adhesion. Polymorphisms in this gene are responsible for the Scianna/Radin blood group system. Two transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Jul 2008]

ERMAP links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0041495264).

BP6

Variant 1-42830524-C-T is Benign according to our data. Variant chr1-42830524-C-T is described in ClinVar as [Benign]. Clinvar id is 3060859.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.285 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ERMAP	NM_001017922.2 linkuse as main transcript	c.76C>T	p.His26Tyr	missense_variant	3/12	ENST00000372517.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ERMAP	ENST00000372517.8 linkuse as main transcript	c.76C>T	p.His26Tyr	missense_variant	3/12	1	NM_001017922.2	P1

Frequencies

GnomAD3 genomes

AF:

0.212

AC:

32257

AN:

152024

Hom.:

4384

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0599

Gnomad AMI

AF:

0.258

Gnomad AMR

AF:

0.251

Gnomad ASJ

AF:

0.214

Gnomad EAS

AF:

0.0143

Gnomad SAS

AF:

0.197

Gnomad FIN

AF:

0.357

Gnomad MID

AF:

0.269

Gnomad NFE

AF:

0.289

Gnomad OTH

AF:

0.221

GnomAD3 exomes

AF:

0.244

AC:

61305

AN:

251350

Hom.:

8652

AF XY:

0.245

AC XY:

33242

AN XY:

135842

show subpopulations

Gnomad AFR exome

AF:

0.0579

Gnomad AMR exome

AF:

0.287

Gnomad ASJ exome

AF:

0.204

Gnomad EAS exome

AF:

0.0161

Gnomad SAS exome

AF:

0.196

Gnomad FIN exome

AF:

0.374

Gnomad NFE exome

AF:

0.286

Gnomad OTH exome

AF:

0.255

GnomAD4 exome

AF:

0.265

AC:

387461

AN:

1459940

Hom.:

54464

Cov.:

AF XY:

0.264

AC XY:

192065

AN XY:

726374

show subpopulations

Gnomad4 AFR exome

AF:

0.0525

Gnomad4 AMR exome

AF:

0.284

Gnomad4 ASJ exome

AF:

0.206

Gnomad4 EAS exome

AF:

0.0173

Gnomad4 SAS exome

AF:

0.201

Gnomad4 FIN exome

AF:

0.371

Gnomad4 NFE exome

AF:

0.283

Gnomad4 OTH exome

AF:

0.238

GnomAD4 genome

AF:

0.212

AC:

32258

AN:

152142

Hom.:

4385

Cov.:

AF XY:

0.214

AC XY:

15941

AN XY:

74362

show subpopulations

Gnomad4 AFR

AF:

0.0597

Gnomad4 AMR

AF:

0.251

Gnomad4 ASJ

AF:

0.214

Gnomad4 EAS

AF:

0.0143

Gnomad4 SAS

AF:

0.197

Gnomad4 FIN

AF:

0.357

Gnomad4 NFE

AF:

0.289

Gnomad4 OTH

AF:

0.218

Alfa

AF:

0.264

Hom.:

11820

Bravo

AF:

0.196

TwinsUK

AF:

0.290

AC:

1076

ALSPAC

AF:

0.283

AC:

1092

ESP6500AA

AF:

0.0697

AC:

307

ESP6500EA

AF:

0.278

AC:

2391

ExAC

AF:

0.241

AC:

29321

Asia WGS

AF:

0.0880

AC:

308

AN:

3478

EpiCase

AF:

0.279

EpiControl

AF:

0.280

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

ERMAP-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 21, 2019

This variant is classified as 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

0.088

BayesDel_addAF

Benign

-0.78

BayesDel_noAF

Benign

-0.74

CADD

Benign

4.4

DANN

Benign

0.54

DEOGEN2

Benign

0.0074

T;T

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.033

LIST_S2

Benign

0.31

.;T

MetaRNN

Benign

0.0041

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.55

N;N

MutationTaster

Benign

1.0

P;P;P

PrimateAI

Benign

0.32

PROVEAN

Benign

-1.0

N;N

REVEL

Benign

0.078

Sift

Benign

0.64

T;T

Sift4G

Benign

0.94

T;T

Polyphen

0.39

B;B

Vest4

0.061

MPC

0.17

ClinPred

0.0086

GERP RS

0.71

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.038

gMVP

0.29

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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