NM_000139.5:c.710A>G

Variant names:

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_000139.5(MS4A2):c.710A>G(p.Glu237Gly) variant causes a missense change. The variant allele was found at a frequency of 0.0357 in 1,608,858 control chromosomes in the GnomAD database, including 2,535 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.073 ( 831 hom., cov: 32)

Exomes 𝑓: 0.032 ( 1704 hom. )

Consequence

MS4A2
NM_000139.5 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 3.59

Publications

87 publications found

Variant links:

Genes affected

MS4A2 (HGNC:7316): (membrane spanning 4-domains A2) The allergic response involves the binding of allergen to receptor-bound IgE followed by cell activation and the release of mediators responsible for the manifestations of allergy. The IgE-receptor, a tetramer composed of an alpha, beta, and 2 disulfide-linked gamma chains, is found on the surface of mast cells and basophils. This gene encodes the beta subunit of the high affinity IgE receptor which is a member of the membrane-spanning 4A gene family. Members of this nascent protein family are characterized by common structural features and similar intron/exon splice boundaries and display unique expression patterns among hematopoietic cells and nonlymphoid tissues. This family member is localized to 11q12, among a cluster of membrane-spanning 4A gene family members. Alternative splicing results in multiple transcript variants encoding distinct proteins. Additional transcript variants have been described but require experimental validation. [provided by RefSeq, Mar 2012]

MS4A2 Gene-Disease associations (from GenCC):

IgE responsiveness, atopic
Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

MS4A2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=9.176135E-4).

BP6

Variant 11-60095631-A-G is Benign according to our data. Variant chr11-60095631-A-G is described in ClinVar as Benign. ClinVar VariationId is 14807.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.179 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000139.5. 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
	MS4A2	NM_000139.5	MANE Select	c.710A>G	p.Glu237Gly	missense	Exon 7 of 7	NP_000130.1
	MS4A2	NM_001256916.2		c.575A>G	p.Glu192Gly	missense	Exon 6 of 6	NP_001243845.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MS4A2	ENST00000278888.8	TSL:1 MANE Select	c.710A>G	p.Glu237Gly	missense	Exon 7 of 7	ENSP00000278888.3
	MS4A2	ENST00000617306.1	TSL:1	c.575A>G	p.Glu192Gly	missense	Exon 6 of 6	ENSP00000482594.1

Frequencies

GnomAD3 genomes

AF:

0.0729

AC:

11084

AN:

152148

Hom.:

829

Cov.:

show subpopulations

Gnomad AFR

AF:

0.182

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0351

Gnomad ASJ

AF:

0.0801

Gnomad EAS

AF:

0.170

Gnomad SAS

AF:

0.0480

Gnomad FIN

AF:

0.00122

Gnomad MID

AF:

0.0696

Gnomad NFE

AF:

0.0212

Gnomad OTH

AF:

0.0633

GnomAD2 exomes

AF:

0.0470

AC:

11814

AN:

251444

AF XY:

0.0441

show subpopulations

Gnomad AFR exome

AF:

0.182

Gnomad AMR exome

AF:

0.0240

Gnomad ASJ exome

AF:

0.0757

Gnomad EAS exome

AF:

0.176

Gnomad FIN exome

AF:

0.00129

Gnomad NFE exome

AF:

0.0208

Gnomad OTH exome

AF:

0.0391

GnomAD4 exome

AF:

0.0318

AC:

46367

AN:

1456592

Hom.:

1704

Cov.:

AF XY:

0.0316

AC XY:

22928

AN XY:

725096

show subpopulations

African (AFR)

AF:

0.185

AC:

6162

AN:

33254

American (AMR)

AF:

0.0250

AC:

1119

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.0745

AC:

1944

AN:

26078

East Asian (EAS)

AF:

0.162

AC:

6424

AN:

39644

South Asian (SAS)

AF:

0.0425

AC:

3661

AN:

86174

European-Finnish (FIN)

AF:

0.00234

AC:

125

AN:

53412

Middle Eastern (MID)

AF:

0.0459

AC:

264

AN:

5752

European-Non Finnish (NFE)

AF:

0.0214

AC:

23725

AN:

1107372

Other (OTH)

AF:

0.0489

AC:

2943

AN:

60190

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.459

Heterozygous variant carriers

2052

4104

6156

8208

10260

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1122

2244

3366

4488

5610

<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:

0.0729

AC:

11096

AN:

152266

Hom.:

831

Cov.:

AF XY:

0.0711

AC XY:

5292

AN XY:

74452

show subpopulations

African (AFR)

AF:

0.182

AC:

7566

AN:

41522

American (AMR)

AF:

0.0350

AC:

536

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.0801

AC:

278

AN:

3470

East Asian (EAS)

AF:

0.170

AC:

880

AN:

5186

South Asian (SAS)

AF:

0.0476

AC:

230

AN:

4828

European-Finnish (FIN)

AF:

0.00122

AC:

AN:

10630

Middle Eastern (MID)

AF:

0.0680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0212

AC:

1443

AN:

68012

Other (OTH)

AF:

0.0617

AC:

130

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

495

990

1484

1979

2474

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

112

224

336

448

560

<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:

0.0428

Hom.:

1417

Bravo

AF:

0.0805

TwinsUK

AF:

0.0197

AC:

ALSPAC

AF:

0.0200

AC:

ESP6500AA

AF:

0.171

AC:

752

ESP6500EA

AF:

0.0231

AC:

198

ExAC

AF:

0.0484

AC:

5881

Asia WGS

AF:

0.116

AC:

402

AN:

3478

EpiCase

AF:

0.0255

EpiControl

AF:

0.0256

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

RECLASSIFIED - MYOC POLYMORPHISM

Benign:1

Sep 01, 2001

OMIM

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:literature only

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.093

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.51

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.34

Eigen

Benign

-0.069

Eigen_PC

Benign

-0.19

FATHMM_MKL

Benign

0.16

LIST_S2

Benign

0.46

MetaRNN

Benign

0.00092

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.5

PhyloP100

3.6

PrimateAI

Benign

0.34

PROVEAN

Uncertain

-3.8

REVEL

Benign

0.12

Sift

Uncertain

0.0020

Sift4G

Uncertain

0.014

Polyphen

0.95

Vest4

0.075

MPC

0.083

ClinPred

0.060

GERP RS

4.8

Varity_R

0.14

gMVP

0.40

Mutation Taster

=94/6

polymorphism (auto)

(source)

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

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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over