rs1855699366

Variant names:

• chr11-60088812-A-C
• rs1855699366
• NM_000139.5:c.47A>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_000139.5(MS4A2):​c.47A>C​(p.Glu16Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: MS4A2 NM_000139.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.23
• Publications: 0 publications found

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)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09562817).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MS4A2	NM_000139.5	MANE Select	c.47A>C	p.Glu16Ala	missense	Exon 1 of 7	NP_000130.1	Q01362
	MS4A2	NM_001256916.2		c.47A>C	p.Glu16Ala	missense	Exon 1 of 6	NP_001243845.1	A0A0B4J2E9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MS4A2	ENST00000278888.8	TSL:1 MANE Select	c.47A>C	p.Glu16Ala	missense	Exon 1 of 7	ENSP00000278888.3	Q01362
	MS4A2	ENST00000617306.1	TSL:1	c.47A>C	p.Glu16Ala	missense	Exon 1 of 6	ENSP00000482594.1	A0A0B4J2E9
	MS4A2	ENST00000440896.2	TSL:1	n.149A>C		non_coding_transcript_exon	Exon 1 of 5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000370 Hom.: 0

Bravo AF: 0.0000113

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.076	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	0.065
DANN	Benign	0.57
DEOGEN2	Benign	0.088	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.015	N
LIST_S2	Benign	0.57	T
M_CAP	Benign	0.029	D
MetaRNN	Benign	0.096	T
MetaSVM	Benign	-0.80	T
MutationAssessor	Benign	1.1	L
PhyloP100		-1.2
PrimateAI	Benign	0.26	T
PROVEAN	Pathogenic	-5.8	D
REVEL	Benign	0.15
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.30	B
Vest4		0.16
MVP		0.50
MPC		0.021
ClinPred		0.96	D
GERP RS		-8.8
PromoterAI		-0.018	Neutral
Varity_R		0.038
gMVP		0.16
Mutation Taster		=99/1	polymorphism

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

Other links and lift over

dbSNP: rs1855699366; hg19: chr11-59856285;