rs33953680

Variant names:

• chr1-42830524-C-T
• rs33953680
• NM_001017922.2:c.76C>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.21 (4385 hom., cov: 31)
  • Exomes 𝑓: 0.27 (54464 hom.)
• Consequence: ERMAP NM_001017922.2 missense
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: -0.177
• Publications: 34 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 -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 VariationId 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.

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.76C>T	p.His26Tyr	missense	Exon 3 of 12	NP_001017922.1	Q96PL5
	ERMAP	NM_018538.4		c.76C>T	p.His26Tyr	missense	Exon 2 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.76C>T	p.His26Tyr	missense	Exon 3 of 12	ENSP00000361595.2	Q96PL5
	ERMAP	ENST00000372514.7	TSL:1	c.76C>T	p.His26Tyr	missense	Exon 2 of 11	ENSP00000361592.3	Q96PL5
	ERMAP	ENST00000328249.3	TSL:1	n.610C>T		non_coding_transcript_exon	Exon 1 of 9

Frequencies

GnomAD3 genomes AF: 0.212 AC: 32257 AN: 152024 Hom.: 4384 Cov.: 31

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

GnomAD2 exomes AF: 0.244 AC: 61305 AN: 251350 AF XY: 0.245

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 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.: 36 AF XY: 0.264 AC XY: 192065 AN XY: 726374

African (AFR) AF: 0.0525 AC: 1759 AN: 33474

American (AMR) AF: 0.284 AC: 12691 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.206 AC: 5386 AN: 26118

East Asian (EAS) AF: 0.0173 AC: 685 AN: 39700

South Asian (SAS) AF: 0.201 AC: 17331 AN: 86228

European-Finnish (FIN) AF: 0.371 AC: 19786 AN: 53368

Middle Eastern (MID) AF: 0.246 AC: 1419 AN: 5766

European-Non Finnish (NFE) AF: 0.283 AC: 314039 AN: 1110242

Other (OTH) AF: 0.238 AC: 14365 AN: 60326

GnomAD4 genome AF: 0.212 AC: 32258 AN: 152142 Hom.: 4385 Cov.: 31 AF XY: 0.214 AC XY: 15941 AN XY: 74362

African (AFR) AF: 0.0597 AC: 2482 AN: 41552

American (AMR) AF: 0.251 AC: 3829 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.214 AC: 740 AN: 3466

East Asian (EAS) AF: 0.0143 AC: 74 AN: 5170

South Asian (SAS) AF: 0.197 AC: 952 AN: 4822

European-Finnish (FIN) AF: 0.357 AC: 3771 AN: 10562

Middle Eastern (MID) AF: 0.276 AC: 81 AN: 294

European-Non Finnish (NFE) AF: 0.289 AC: 19635 AN: 67978

Other (OTH) AF: 0.218 AC: 460 AN: 2112

Alfa AF: 0.253 Hom.: 15851

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

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	0.088
BayesDel_addAF	Benign	-0.78	T
BayesDel_noAF	Benign	-0.74
CADD	Benign	4.4
DANN	Benign	0.54
DEOGEN2	Benign	0.0074	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.033	N
LIST_S2	Benign	0.31	T
MetaRNN	Benign	0.0041	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.55	N
PhyloP100		-0.18
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-1.0	N
REVEL	Benign	0.078
Sift	Benign	0.64	T
Sift4G	Benign	0.94	T
Polyphen		0.39	B
Vest4		0.061
MPC		0.17
ClinPred		0.0086	T
GERP RS		0.71
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.038
gMVP		0.29
Mutation Taster		=276/24	polymorphism (auto)

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

Other links and lift over

dbSNP: rs33953680; hg19: chr1-43296195; COSMIC: COSV60274464; COSMIC: COSV60274464;