chr1-42830899-C-T

Variant names:

• chr1-42830899-C-T
• rs149787850
• NM_001017922.2:c.217C>T

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Strong BP6 BS2

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. 14/21 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. R73L) 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
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: -1.20
• Publications: 6 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -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 VariationId is 3058643.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS2: High Homozygotes in GnomAd4 at 3 BG gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001017922.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ERMAP	NM_001017922.2	MANE Select	c.217C>T	p.Arg73Cys	missense	Exon 4 of 12	NP_001017922.1	Q96PL5
	ERMAP	NM_018538.4		c.217C>T	p.Arg73Cys	missense	Exon 3 of 11	NP_061008.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ERMAP	ENST00000372517.8	TSL:1 MANE Select	c.217C>T	p.Arg73Cys	missense	Exon 4 of 12	ENSP00000361595.2	Q96PL5
	ERMAP	ENST00000372514.7	TSL:1	c.217C>T	p.Arg73Cys	missense	Exon 3 of 11	ENSP00000361592.3	Q96PL5
	ERMAP	ENST00000328249.3	TSL:1	n.985C>T		non_coding_transcript_exon	Exon 1 of 9

Frequencies

GnomAD3 genomes AF: 0.00272 AC: 414 AN: 152124 Hom.: 3 Cov.: 32

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

GnomAD2 exomes AF: 0.000614 AC: 154 AN: 250812 AF XY: 0.000361

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 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

African (AFR) AF: 0.00878 AC: 294 AN: 33478

American (AMR) AF: 0.000448 AC: 20 AN: 44686

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.0000756 AC: 3 AN: 39692

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86220

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53410

Middle Eastern (MID) AF: 0.000520 AC: 3 AN: 5768

European-Non Finnish (NFE) AF: 0.0000207 AC: 23 AN: 1111932

Other (OTH) AF: 0.000696 AC: 42 AN: 60382

GnomAD4 genome AF: 0.00273 AC: 415 AN: 152242 Hom.: 3 Cov.: 32 AF XY: 0.00231 AC XY: 172 AN XY: 74452

African (AFR) AF: 0.00949 AC: 394 AN: 41536

American (AMR) AF: 0.000916 AC: 14 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5170

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68022

Other (OTH) AF: 0.00285 AC: 6 AN: 2108

Alfa AF: 0.000974 Hom.: 1

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

ClinVar submissions

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	ERMAP-related disorder (1)

Computational scores

Source: dbNSFP v4.9

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
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
MetaSVM	Benign	-0.85	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		-1.2
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.17
Sift	Benign	0.10	T
Sift4G	Benign	0.11	T
Polyphen		0.96	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
Mutation Taster		=95/5	polymorphism

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

Other links and lift over

dbSNP: rs149787850; hg19: chr1-43296570;