Genetic Variant NM_001017922.2:c.11C>T (chr1-42830459-C-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001017922.2(ERMAP):c.11C>T(p.Ala4Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00312 in 1,614,044 control chromosomes in the GnomAD database, including 144 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 (★★).

Frequency

Genomes: 𝑓 0.016 ( 71 hom., cov: 32)

Exomes 𝑓: 0.0018 ( 73 hom. )

Consequence

ERMAP
NM_001017922.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.01

Publications

7 publications found

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 was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0021736622).

BP6

Variant 1-42830459-C-T is Benign according to our data. Variant chr1-42830459-C-T is described in ClinVar as Benign. ClinVar VariationId is 775539.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0523 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.11C>T	p.Ala4Val	missense	Exon 3 of 12	NP_001017922.1	Q96PL5
	ERMAP	NM_018538.4		c.11C>T	p.Ala4Val	missense	Exon 2 of 11	NP_061008.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ERMAP	ENST00000372517.8	TSL:1 MANE Select	c.11C>T	p.Ala4Val	missense	Exon 3 of 12	ENSP00000361595.2	Q96PL5
ERMAP	ENST00000372514.7	TSL:1	c.11C>T	p.Ala4Val	missense	Exon 2 of 11	ENSP00000361592.3	Q96PL5
ERMAP	ENST00000328249.3	TSL:1	n.545C>T		non_coding_transcript_exon	Exon 1 of 9

Frequencies

GnomAD3 genomes

AF:

0.0157

AC:

2384

AN:

152090

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0541

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00661

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000943

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.000250

Gnomad OTH

AF:

0.0100

GnomAD2 exomes

AF:

0.00429

AC:

1078

AN:

251474

AF XY:

0.00336

show subpopulations

Gnomad AFR exome

AF:

0.0552

Gnomad AMR exome

AF:

0.00309

Gnomad ASJ exome

AF:

0.0000992

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000185

Gnomad NFE exome

AF:

0.000457

Gnomad OTH exome

AF:

0.00228

GnomAD4 exome

AF:

0.00181

AC:

2650

AN:

1461836

Hom.:

Cov.:

AF XY:

0.00158

AC XY:

1152

AN XY:

727220

show subpopulations

African (AFR)

AF:

0.0585

AC:

1957

AN:

33468

American (AMR)

AF:

0.00362

AC:

162

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.000116

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.000168

AC:

AN:

53416

Middle Eastern (MID)

AF:

0.00364

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000235

AC:

261

AN:

1111974

Other (OTH)

AF:

0.00381

AC:

230

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.447

Heterozygous variant carriers

121

243

364

486

607

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

140

210

280

350

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0157

AC:

2391

AN:

152208

Hom.:

Cov.:

AF XY:

0.0154

AC XY:

1149

AN XY:

74398

show subpopulations

African (AFR)

AF:

0.0542

AC:

2249

AN:

41518

American (AMR)

AF:

0.00654

AC:

100

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5178

South Asian (SAS)

AF:

0.00

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.0000943

AC:

AN:

10610

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000250

AC:

AN:

68000

Other (OTH)

AF:

0.00993

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

112

224

335

447

559

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00517

Hom.:

Bravo

AF:

0.0180

ESP6500AA

AF:

0.0449

AC:

198

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.00491

AC:

596

Asia WGS

AF:

0.00433

AC:

AN:

3478

EpiCase

AF:

0.000545

EpiControl

AF:

0.000415

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.26

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.65

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0092

Eigen

Benign

-0.64

Eigen_PC

Benign

-0.58

FATHMM_MKL

Benign

0.59

LIST_S2

Benign

0.46

MetaRNN

Benign

0.0022

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.90

PhyloP100

1.0

PrimateAI

Benign

0.34

PROVEAN

Benign

-1.6

REVEL

Benign

0.040

Sift

Uncertain

0.016

Sift4G

Uncertain

0.031

Polyphen

0.052

Vest4

0.12

MVP

0.30

MPC

0.24

ClinPred

0.016

GERP RS

2.2

Varity_R

0.082

gMVP

0.41

Mutation Taster

=98/2

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.12

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over