chr1-42830860-C-G

Variant names:

• chr1-42830860-C-G
• rs56136737
• NM_001017922.2:c.178C>G

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The ENST00000372517.8(ERMAP):​c.178C>G​(p.Pro60Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00052 in 1,611,120 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Affects (no stars).

• Frequency:
  • Genomes: 𝑓 0.00043 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00053 (2 hom.)
• Consequence: ERMAP ENST00000372517.8 missense
• Clinical Significance: Affects no assertion criteria provided O:1
• Conservation: PhyloP100: -0.0380
• Publications: 8 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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.13521188).
• BS2: High Homozygotes in GnomAdExome4 at 2 BG gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000372517.8. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ERMAP	NM_001017922.2	MANE Select	c.178C>G	p.Pro60Ala	missense	Exon 4 of 12	NP_001017922.1
	ERMAP	NM_018538.4		c.178C>G	p.Pro60Ala	missense	Exon 3 of 11	NP_061008.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ERMAP	ENST00000372517.8	TSL:1 MANE Select	c.178C>G	p.Pro60Ala	missense	Exon 4 of 12	ENSP00000361595.2
	ERMAP	ENST00000372514.7	TSL:1	c.178C>G	p.Pro60Ala	missense	Exon 3 of 11	ENSP00000361592.3
	ERMAP	ENST00000328249.3	TSL:1	n.946C>G		non_coding_transcript_exon	Exon 1 of 9

Frequencies

GnomAD3 genomes AF: 0.000427 AC: 65 AN: 152160 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00346

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000848

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000632

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000650 AC: 159 AN: 244722 AF XY: 0.000726

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000354

Gnomad ASJ exome AF: 0.00171

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000287

Gnomad NFE exome AF: 0.00107

Gnomad OTH exome AF: 0.000831

GnomAD4 exome AF: 0.000530 AC: 773 AN: 1458842 Hom.: 2 Cov.: 32 AF XY: 0.000549 AC XY: 398 AN XY: 725496

African (AFR) AF: 0.00 AC: 0 AN: 33412

American (AMR) AF: 0.000498 AC: 22 AN: 44198

Ashkenazi Jewish (ASJ) AF: 0.00234 AC: 61 AN: 26056

East Asian (EAS) AF: 0.00 AC: 0 AN: 39550

South Asian (SAS) AF: 0.0000467 AC: 4 AN: 85742

European-Finnish (FIN) AF: 0.000451 AC: 24 AN: 53198

Middle Eastern (MID) AF: 0.000347 AC: 2 AN: 5762

European-Non Finnish (NFE) AF: 0.000570 AC: 633 AN: 1110648

Other (OTH) AF: 0.000448 AC: 27 AN: 60276

GnomAD4 genome AF: 0.000427 AC: 65 AN: 152278 Hom.: 0 Cov.: 32 AF XY: 0.000403 AC XY: 30 AN XY: 74450

African (AFR) AF: 0.0000241 AC: 1 AN: 41568

American (AMR) AF: 0.00 AC: 0 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00346 AC: 12 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.000848 AC: 9 AN: 10616

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

European-Non Finnish (NFE) AF: 0.000632 AC: 43 AN: 68022

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.000670 Hom.: 0

Bravo AF: 0.000400

TwinsUK AF: 0.000539 AC: 2

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.000454 AC: 2

ESP6500EA AF: 0.000581 AC: 5

ExAC AF: 0.000692 AC: 84

ClinVar

ClinVar submissions as Germline

Significance: Affects

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	-	RADIN BLOOD GROUP ANTIGEN (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.58	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	2.7
DANN	Benign	0.63
DEOGEN2	Benign	0.0031	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.078	N
LIST_S2	Benign	0.48	T
M_CAP	Benign	0.0038	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.3	L
PhyloP100		-0.038
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-0.41	N
REVEL	Benign	0.021
Sift	Benign	0.51	T
Sift4G	Benign	1.0	T
Polyphen		0.033	B
Vest4		0.24
MVP		0.15
MPC		0.13
ClinPred		0.033	T
GERP RS		0.30
Varity_R		0.035
gMVP		0.32
Mutation Taster		=99/1	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: rs56136737; hg19: chr1-43296531; COSMIC: COSV105898828; COSMIC: COSV105898828;