Genetic Variant NM_001017922.2:c.54C>T (chr1-42830502-C-T) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BA1

The NM_001017922.2(ERMAP):c.54C>T(p.Leu18Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.234 in 1,613,398 control chromosomes in the GnomAD database, including 47,097 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars). Synonymous variant affecting the same amino acid position (i.e. L18L) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.20 ( 3663 hom., cov: 32)

Exomes 𝑓: 0.24 ( 43434 hom. )

Consequence

ERMAP
NM_001017922.2 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -1.73

Publications

20 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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.74).

BP6

Variant 1-42830502-C-T is Benign according to our data. Variant chr1-42830502-C-T is described in ClinVar as Benign. ClinVar VariationId is 3058973.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=-1.73 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.25 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.54C>T	p.Leu18Leu	synonymous	Exon 3 of 12	NP_001017922.1	Q96PL5
	ERMAP	NM_018538.4		c.54C>T	p.Leu18Leu	synonymous	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.54C>T	p.Leu18Leu	synonymous	Exon 3 of 12	ENSP00000361595.2	Q96PL5
ERMAP	ENST00000372514.7	TSL:1	c.54C>T	p.Leu18Leu	synonymous	Exon 2 of 11	ENSP00000361592.3	Q96PL5
ERMAP	ENST00000328249.3	TSL:1	n.588C>T		non_coding_transcript_exon	Exon 1 of 9

Frequencies

GnomAD3 genomes

AF:

0.204

AC:

31043

AN:

152006

Hom.:

3663

Cov.:

show subpopulations

Gnomad AFR

AF:

0.111

Gnomad AMI

AF:

0.114

Gnomad AMR

AF:

0.232

Gnomad ASJ

AF:

0.178

Gnomad EAS

AF:

0.0139

Gnomad SAS

AF:

0.175

Gnomad FIN

AF:

0.339

Gnomad MID

AF:

0.196

Gnomad NFE

AF:

0.253

Gnomad OTH

AF:

0.203

GnomAD2 exomes

AF:

0.224

AC:

56235

AN:

251416

AF XY:

0.223

show subpopulations

Gnomad AFR exome

AF:

0.111

Gnomad AMR exome

AF:

0.269

Gnomad ASJ exome

AF:

0.179

Gnomad EAS exome

AF:

0.0160

Gnomad FIN exome

AF:

0.353

Gnomad NFE exome

AF:

0.251

Gnomad OTH exome

AF:

0.227

GnomAD4 exome

AF:

0.238

AC:

347185

AN:

1461274

Hom.:

43434

Cov.:

AF XY:

0.236

AC XY:

171801

AN XY:

726964

show subpopulations

African (AFR)

AF:

0.109

AC:

3644

AN:

33476

American (AMR)

AF:

0.266

AC:

11901

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.178

AC:

4650

AN:

26134

East Asian (EAS)

AF:

0.0172

AC:

681

AN:

39700

South Asian (SAS)

AF:

0.179

AC:

15474

AN:

86244

European-Finnish (FIN)

AF:

0.350

AC:

18693

AN:

53398

Middle Eastern (MID)

AF:

0.188

AC:

1082

AN:

5766

European-Non Finnish (NFE)

AF:

0.250

AC:

278055

AN:

1111458

Other (OTH)

AF:

0.215

AC:

13005

AN:

60376

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

14431

28862

43292

57723

72154

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9138

18276

27414

36552

45690

<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:

0.204

AC:

31052

AN:

152124

Hom.:

3663

Cov.:

AF XY:

0.206

AC XY:

15343

AN XY:

74346

show subpopulations

African (AFR)

AF:

0.111

AC:

4609

AN:

41514

American (AMR)

AF:

0.232

AC:

3550

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.178

AC:

618

AN:

3470

East Asian (EAS)

AF:

0.0139

AC:

AN:

5168

South Asian (SAS)

AF:

0.175

AC:

845

AN:

4820

European-Finnish (FIN)

AF:

0.339

AC:

3584

AN:

10562

Middle Eastern (MID)

AF:

0.187

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.253

AC:

17192

AN:

67992

Other (OTH)

AF:

0.201

AC:

423

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1230

2460

3690

4920

6150

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

328

656

984

1312

1640

<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:

0.230

Hom.:

12575

Bravo

AF:

0.191

Asia WGS

AF:

0.0860

AC:

298

AN:

3478

EpiCase

AF:

0.241

EpiControl

AF:

0.244

ClinVar

ClinVar submissions

Significance:Benign

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

ERMAP-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.74

CADD

Benign

0.52

(source)

DANN

Benign

0.68

PhyloP100

-1.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=300/0

polymorphism (auto)

(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

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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