11-60093449-C-T

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_000139.5(MS4A2):c.428C>T(p.Thr143Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00286 in 1,614,104 control chromosomes in the GnomAD database, including 113 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.014 ( 61 hom., cov: 32)

Exomes 𝑓: 0.0017 ( 52 hom. )

Consequence

MS4A2
NM_000139.5 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: -4.22

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0053468943).

BP6

Variant 11-60093449-C-T is Benign according to our data. Variant chr11-60093449-C-T is described in ClinVar as [Benign]. Clinvar id is 768452.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0143 (2182/152216) while in subpopulation AFR AF= 0.0492 (2042/41510). AF 95% confidence interval is 0.0474. There are 61 homozygotes in gnomad4. There are 998 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 61 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MS4A2	NM_000139.5 link	c.428C>T	p.Thr143Met	missense_variant	Exon 5 of 7	ENST00000278888.8	NP_000130.1	Q01362

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
MS4A2	ENST00000278888.8 link	c.428C>T	p.Thr143Met	missense_variant	Exon 5 of 7	1	NM_000139.5	ENSP00000278888.3	Q01362
MS4A2	ENST00000617306.1 link	c.293C>T	p.Thr98Met	missense_variant	Exon 4 of 6	1		ENSP00000482594.1	A0A0B4J2E9
MS4A2	ENST00000440896.2 link	n.530C>T		non_coding_transcript_exon_variant	Exon 5 of 5	1

Frequencies

GnomAD3 genomes

AF:

0.0143

AC:

2178

AN:

152098

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0492

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00589

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000353

Gnomad OTH

AF:

0.0124

GnomAD3 exomes

AF:

0.00395

AC:

992

AN:

251454

Hom.:

AF XY:

0.00274

AC XY:

372

AN XY:

135902

show subpopulations

Gnomad AFR exome

AF:

0.0496

Gnomad AMR exome

AF:

0.00286

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000163

Gnomad SAS exome

AF:

0.000719

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000378

Gnomad OTH exome

AF:

0.00310

GnomAD4 exome

AF:

0.00166

AC:

2428

AN:

1461888

Hom.:

Cov.:

AF XY:

0.00148

AC XY:

1077

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.0520

Gnomad4 AMR exome

AF:

0.00277

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000126

Gnomad4 SAS exome

AF:

0.000556

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000244

Gnomad4 OTH exome

AF:

0.00371

GnomAD4 genome

AF:

0.0143

AC:

2182

AN:

152216

Hom.:

Cov.:

AF XY:

0.0134

AC XY:

998

AN XY:

74432

show subpopulations

Gnomad4 AFR

AF:

0.0492

Gnomad4 AMR

AF:

0.00582

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000353

Gnomad4 OTH

AF:

0.0123

Alfa

AF:

0.00285

Hom.:

Bravo

AF:

0.0166

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.0513

AC:

226

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.00455

AC:

552

Asia WGS

AF:

0.00520

AC:

AN:

3478

EpiCase

AF:

0.000382

EpiControl

AF:

0.000533

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jun 29, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.085

BayesDel_addAF

Benign

-0.75

BayesDel_noAF

Benign

-0.81

CADD

Benign

0.0050

DANN

Benign

0.76

DEOGEN2

Benign

0.068

T;.

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.0028

LIST_S2

Benign

0.32

T;T

MetaRNN

Benign

0.0053

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.7

L;.

PrimateAI

Benign

0.30

PROVEAN

Benign

-1.1

N;.

REVEL

Benign

0.053

Sift

Benign

0.32

T;.

Sift4G

Benign

0.27

T;T

Polyphen

0.20

B;.

Vest4

0.28

MVP

0.21

MPC

0.022

ClinPred

0.010

GERP RS

-8.3

Varity_R

0.036

gMVP

0.18

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over