Genetic Variant MS4A2:c.*124C>T (chr11-60095780-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000139.5(MS4A2):c.*124C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0388 in 714,882 control chromosomes in the GnomAD database, including 1,142 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.052 ( 382 hom., cov: 32)

Exomes 𝑓: 0.035 ( 760 hom. )

Consequence

MS4A2
NM_000139.5 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.742

Publications

18 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.16 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
MS4A2	NM_000139.5 link	c.*124C>T	3_prime_UTR_variant	Exon 7 of 7	ENST00000278888.8	NP_000130.1
MS4A2	NM_001256916.2 link	c.*124C>T	3_prime_UTR_variant	Exon 6 of 6		NP_001243845.1
MS4A2	XM_005273846.5 link	c.*124C>T	3_prime_UTR_variant	Exon 8 of 8		XP_005273903.1
MS4A2	XM_011544850.3 link	c.*124C>T	3_prime_UTR_variant	Exon 8 of 8		XP_011543152.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MS4A2	ENST00000278888.8 link	c.*124C>T		3_prime_UTR_variant	Exon 7 of 7	1	NM_000139.5	ENSP00000278888.3
MS4A2	ENST00000617306.1 link	c.*124C>T		3_prime_UTR_variant	Exon 6 of 6	1		ENSP00000482594.1

Frequencies

GnomAD3 genomes

AF:

0.0522

AC:

7935

AN:

152026

Hom.:

380

Cov.:

show subpopulations

Gnomad AFR

AF:

0.111

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0280

Gnomad ASJ

AF:

0.0798

Gnomad EAS

AF:

0.169

Gnomad SAS

AF:

0.0485

Gnomad FIN

AF:

0.00123

Gnomad MID

AF:

0.0633

Gnomad NFE

AF:

0.0208

Gnomad OTH

AF:

0.0460

GnomAD4 exome

AF:

0.0351

AC:

19769

AN:

562738

Hom.:

760

Cov.:

AF XY:

0.0353

AC XY:

10716

AN XY:

303858

show subpopulations

African (AFR)

AF:

0.105

AC:

1619

AN:

15386

American (AMR)

AF:

0.0225

AC:

754

AN:

33550

Ashkenazi Jewish (ASJ)

AF:

0.0732

AC:

1435

AN:

19602

East Asian (EAS)

AF:

0.158

AC:

5040

AN:

31914

South Asian (SAS)

AF:

0.0413

AC:

2529

AN:

61296

European-Finnish (FIN)

AF:

0.00234

AC:

105

AN:

44864

Middle Eastern (MID)

AF:

0.0433

AC:

174

AN:

4016

European-Non Finnish (NFE)

AF:

0.0210

AC:

6752

AN:

321618

Other (OTH)

AF:

0.0446

AC:

1361

AN:

30492

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

835

1671

2506

3342

4177

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

128

256

384

512

640

<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:

0.0522

AC:

7939

AN:

152144

Hom.:

382

Cov.:

AF XY:

0.0512

AC XY:

3808

AN XY:

74384

show subpopulations

African (AFR)

AF:

0.111

AC:

4585

AN:

41482

American (AMR)

AF:

0.0279

AC:

427

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.0798

AC:

277

AN:

3470

East Asian (EAS)

AF:

0.169

AC:

878

AN:

5182

South Asian (SAS)

AF:

0.0481

AC:

232

AN:

4820

European-Finnish (FIN)

AF:

0.00123

AC:

AN:

10592

Middle Eastern (MID)

AF:

0.0612

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0208

AC:

1415

AN:

67998

Other (OTH)

AF:

0.0446

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

368

736

1103

1471

1839

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

172

258

344

430

<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:

0.0332

Hom.:

693

Bravo

AF:

0.0569

Asia WGS

AF:

0.113

AC:

391

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

2.3

(source)

DANN

Benign

0.39

PhyloP100

-0.74

Mutation Taster

=100/0

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over