rs569108

Variant names:

• chr11-60095631-A-C
• NM_000139.5:c.710A>C

Your query was ambiguous. Multiple possible variants found:

• chr11-60095631-A-C
• chr11-60095631-A-G
• chr11-60095631-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_000139.5(MS4A2):​c.710A>C​(p.Glu237Ala) 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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.59

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]

ACMG classification

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=0.16625583).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MS4A2	NM_000139.5	c.710A>C	p.Glu237Ala	missense_variant	Exon 7 of 7	ENST00000278888.8	NP_000130.1
MS4A2	NM_001256916.2	c.575A>C	p.Glu192Ala	missense_variant	Exon 6 of 6		NP_001243845.1
MS4A2	XM_005273846.5	c.731A>C	p.Glu244Ala	missense_variant	Exon 8 of 8		XP_005273903.1
MS4A2	XM_011544850.3	c.710A>C	p.Glu237Ala	missense_variant	Exon 8 of 8		XP_011543152.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MS4A2	ENST00000278888.8	c.710A>C	p.Glu237Ala	missense_variant	Exon 7 of 7	1	NM_000139.5	ENSP00000278888.3
MS4A2	ENST00000617306.1	c.575A>C	p.Glu192Ala	missense_variant	Exon 6 of 6	1		ENSP00000482594.1

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	0.12
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	18
DANN	Uncertain	0.98
DEOGEN2	Benign	0.19	T;.
Eigen	Benign	-0.14
Eigen_PC	Benign	-0.24
FATHMM_MKL	Benign	0.18	N
LIST_S2	Benign	0.53	T;T
M_CAP	Benign	0.0052	T
MetaRNN	Benign	0.17	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.5	L;.
PrimateAI	Benign	0.35	T
PROVEAN	Uncertain	-3.1	D;.
REVEL	Benign	0.081
Sift	Uncertain	0.0050	D;.
Sift4G	Uncertain	0.031	D;D
Polyphen		0.91	P;.
Vest4		0.17
MutPred		0.19		Loss of disorder (P = 0.1232);.;
MVP		0.68
MPC		0.051
ClinPred		0.75	D
GERP RS		4.8
Varity_R		0.13
gMVP		0.36

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;