chr1-42830899-C-T

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_001017922.2(ERMAP):​c.217C>T​(p.Arg73Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000498 in 1,613,940 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R73H) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0027 ( 3 hom., cov: 32)
Exomes 𝑓: 0.00027 ( 0 hom. )

Consequence

ERMAP
NM_001017922.2 missense

Scores

2
16

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -1.20
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.0063408017).
BP6
Variant 1-42830899-C-T is Benign according to our data. Variant chr1-42830899-C-T is described in ClinVar as [Benign]. Clinvar id is 3058643.Status of the report is no_assertion_criteria_provided, 0 stars.
BS2
High Homozygotes in GnomAd4 at 3 BG gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ERMAPNM_001017922.2 linkc.217C>T p.Arg73Cys missense_variant 4/12 ENST00000372517.8 NP_001017922.1 Q96PL5A0A1C9HIH9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ERMAPENST00000372517.8 linkc.217C>T p.Arg73Cys missense_variant 4/121 NM_001017922.2 ENSP00000361595.2 Q96PL5

Frequencies

GnomAD3 genomes
AF:
0.00272
AC:
414
AN:
152124
Hom.:
3
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00949
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000917
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00288
GnomAD3 exomes
AF:
0.000614
AC:
154
AN:
250812
Hom.:
0
AF XY:
0.000361
AC XY:
49
AN XY:
135588
show subpopulations
Gnomad AFR exome
AF:
0.00821
Gnomad AMR exome
AF:
0.000348
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000163
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000441
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000265
AC:
388
AN:
1461698
Hom.:
0
Cov.:
32
AF XY:
0.000221
AC XY:
161
AN XY:
727152
show subpopulations
Gnomad4 AFR exome
AF:
0.00878
Gnomad4 AMR exome
AF:
0.000448
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000756
Gnomad4 SAS exome
AF:
0.0000232
Gnomad4 FIN exome
AF:
0.0000187
Gnomad4 NFE exome
AF:
0.0000207
Gnomad4 OTH exome
AF:
0.000696
GnomAD4 genome
AF:
0.00273
AC:
415
AN:
152242
Hom.:
3
Cov.:
32
AF XY:
0.00231
AC XY:
172
AN XY:
74452
show subpopulations
Gnomad4 AFR
AF:
0.00949
Gnomad4 AMR
AF:
0.000916
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00285
Alfa
AF:
0.000966
Hom.:
0
Bravo
AF:
0.00318
ESP6500AA
AF:
0.00908
AC:
40
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.000914
AC:
111
Asia WGS
AF:
0.000289
AC:
1
AN:
3478
EpiCase
AF:
0.000164
EpiControl
AF:
0.0000593

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

ERMAP-related disorder Benign:1
Benign, no assertion criteria providedclinical testingPreventionGenetics, part of Exact SciencesFeb 01, 2021This 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
0.22
BayesDel_addAF
Benign
-0.46
T
BayesDel_noAF
Benign
-0.43
CADD
Benign
12
DANN
Uncertain
1.0
DEOGEN2
Benign
0.079
T;T
Eigen
Benign
-0.47
Eigen_PC
Benign
-0.67
FATHMM_MKL
Benign
0.039
N
LIST_S2
Benign
0.60
.;T
MetaRNN
Benign
0.0063
T;T
MetaSVM
Benign
-0.85
T
MutationAssessor
Uncertain
2.3
M;M
PrimateAI
Benign
0.28
T
PROVEAN
Benign
-1.9
N;N
REVEL
Benign
0.17
Sift
Benign
0.10
T;T
Sift4G
Benign
0.11
T;T
Polyphen
0.96
D;D
Vest4
0.35
MVP
0.57
MPC
0.46
ClinPred
0.062
T
GERP RS
-1.9
Varity_R
0.068
gMVP
0.47

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.

Other links and lift over

dbSNP: rs149787850; hg19: chr1-43296570; API