11-60095631-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_000139.5(MS4A2):​c.710A>T​(p.Glu237Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Consequence

MS4A2
NM_000139.5 missense

Scores

4
15

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.59
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.1904149).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MS4A2NM_000139.5 linkc.710A>T p.Glu237Val missense_variant Exon 7 of 7 ENST00000278888.8 NP_000130.1 Q01362
MS4A2NM_001256916.2 linkc.575A>T p.Glu192Val missense_variant Exon 6 of 6 NP_001243845.1 A0A0B4J2E9
MS4A2XM_005273846.5 linkc.731A>T p.Glu244Val missense_variant Exon 8 of 8 XP_005273903.1
MS4A2XM_011544850.3 linkc.710A>T p.Glu237Val missense_variant Exon 8 of 8 XP_011543152.1 Q01362

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MS4A2ENST00000278888.8 linkc.710A>T p.Glu237Val missense_variant Exon 7 of 7 1 NM_000139.5 ENSP00000278888.3 Q01362
MS4A2ENST00000617306.1 linkc.575A>T p.Glu192Val missense_variant Exon 6 of 6 1 ENSP00000482594.1 A0A0B4J2E9

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
28
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.14
BayesDel_addAF
Benign
-0.16
T
BayesDel_noAF
Benign
-0.47
CADD
Benign
19
DANN
Uncertain
0.99
DEOGEN2
Benign
0.34
T;.
Eigen
Benign
-0.023
Eigen_PC
Benign
-0.15
FATHMM_MKL
Benign
0.16
N
LIST_S2
Benign
0.47
T;T
M_CAP
Benign
0.0085
T
MetaRNN
Benign
0.19
T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.5
L;.
PrimateAI
Benign
0.34
T
PROVEAN
Uncertain
-3.5
D;.
REVEL
Benign
0.11
Sift
Uncertain
0.0010
D;.
Sift4G
Uncertain
0.0080
D;D
Polyphen
0.95
P;.
Vest4
0.25
MutPred
0.26
Loss of disorder (P = 0.0318);.;
MVP
0.70
MPC
0.11
ClinPred
0.96
D
GERP RS
4.8
Varity_R
0.20
gMVP
0.46

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-59863104; API