rs2583471

Positions:

• chr11-60094341-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000139.5(MS4A2):​c.636+279G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.309 in 152,164 control chromosomes in the GnomAD database, including 8,789 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 0.31 (8789 hom., cov: 32)
• Consequence: MS4A2 NM_000139.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.125

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.483 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MS4A2	NM_000139.5	c.636+279G>A		intron_variant		ENST00000278888.8	NP_000130.1
MS4A2	NM_001256916.2	c.501+279G>A		intron_variant			NP_001243845.1
MS4A2	XM_005273846.5	c.657+279G>A		intron_variant			XP_005273903.1
MS4A2	XM_011544850.3	c.636+279G>A		intron_variant			XP_011543152.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MS4A2	ENST00000278888.8	c.636+279G>A		intron_variant		1	NM_000139.5	ENSP00000278888	P1
MS4A2	ENST00000617306.1	c.501+279G>A		intron_variant		1		ENSP00000482594

Frequencies

GnomAD3 genomes AF: 0.309 AC: 46977 AN: 152046 Hom.: 8790 Cov.: 32

Gnomad AFR AF: 0.105

Gnomad AMI AF: 0.426

Gnomad AMR AF: 0.299

Gnomad ASJ AF: 0.381

Gnomad EAS AF: 0.208

Gnomad SAS AF: 0.499

Gnomad FIN AF: 0.322

Gnomad MID AF: 0.494

Gnomad NFE AF: 0.420

Gnomad OTH AF: 0.360

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.309 AC: 46987 AN: 152164 Hom.: 8789 Cov.: 32 AF XY: 0.308 AC XY: 22915 AN XY: 74390

Gnomad4 AFR AF: 0.105

Gnomad4 AMR AF: 0.298

Gnomad4 ASJ AF: 0.381

Gnomad4 EAS AF: 0.207

Gnomad4 SAS AF: 0.500

Gnomad4 FIN AF: 0.322

Gnomad4 NFE AF: 0.420

Gnomad4 OTH AF: 0.361

Alfa AF: 0.347 Hom.: 1276

Bravo AF: 0.294

Asia WGS AF: 0.341 AC: 1185 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.91
DANN	Benign	0.39

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

LitVar

Other links and lift over

dbSNP: rs2583471; hg19: chr11-59861814;