NM_000139.5:c.*3046G>A

Variant names:

• chr11-60098702-G-A
• rs502419
• NM_000139.5:c.*3046G>A

Variant summary

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

The NM_000139.5(MS4A2):​c.*3046G>A variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.379 in 152,002 control chromosomes in the GnomAD database, including 11,443 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 0.38 (11443 hom., cov: 32)
• Consequence: MS4A2 NM_000139.5 downstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.452

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=-0.75).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.529 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MS4A2	NM_000139.5	c.*3046G>A		downstream_gene_variant		ENST00000278888.8	NP_000130.1
MS4A2	NM_001256916.2	c.*3046G>A		downstream_gene_variant			NP_001243845.1
MS4A2	XM_005273846.5	c.*3046G>A		downstream_gene_variant			XP_005273903.1
MS4A2	XM_011544850.3	c.*3046G>A		downstream_gene_variant			XP_011543152.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MS4A2	ENST00000278888.8	c.*3046G>A		downstream_gene_variant		1	NM_000139.5	ENSP00000278888.3
MS4A2	ENST00000617306.1	c.*3046G>A		downstream_gene_variant		1		ENSP00000482594.1

Frequencies

GnomAD3 genomes AF: 0.379 AC: 57545 AN: 151884 Hom.: 11441 Cov.: 32

Gnomad AFR AF: 0.276

Gnomad AMI AF: 0.427

Gnomad AMR AF: 0.335

Gnomad ASJ AF: 0.461

Gnomad EAS AF: 0.377

Gnomad SAS AF: 0.546

Gnomad FIN AF: 0.323

Gnomad MID AF: 0.561

Gnomad NFE AF: 0.441

Gnomad OTH AF: 0.424

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

GnomAD4 genome AF: 0.379 AC: 57563 AN: 152002 Hom.: 11443 Cov.: 32 AF XY: 0.377 AC XY: 27977 AN XY: 74282

Gnomad4 AFR AF: 0.276

Gnomad4 AMR AF: 0.334

Gnomad4 ASJ AF: 0.461

Gnomad4 EAS AF: 0.376

Gnomad4 SAS AF: 0.546

Gnomad4 FIN AF: 0.323

Gnomad4 NFE AF: 0.441

Gnomad4 OTH AF: 0.423

Alfa AF: 0.403 Hom.: 2149

Bravo AF: 0.371

Asia WGS AF: 0.456 AC: 1587 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	0.58
DANN	Benign	0.79

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs502419; hg19: chr11-59866175;