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. The variant received -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
• Publications: 15 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: Benign. The variant received -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.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MS4A2	NM_000139.5	MANE Select	c.*3046G>A		downstream_gene	N/A	NP_000130.1
	MS4A2	NM_001256916.2		c.*3046G>A		downstream_gene	N/A	NP_001243845.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MS4A2	ENST00000278888.8	TSL:1 MANE Select	c.*3046G>A		downstream_gene	N/A	ENSP00000278888.3
	MS4A2	ENST00000617306.1	TSL:1	c.*3046G>A		downstream_gene	N/A	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

African (AFR) AF: 0.276 AC: 11453 AN: 41440

American (AMR) AF: 0.334 AC: 5112 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.461 AC: 1597 AN: 3466

East Asian (EAS) AF: 0.376 AC: 1943 AN: 5162

South Asian (SAS) AF: 0.546 AC: 2637 AN: 4828

European-Finnish (FIN) AF: 0.323 AC: 3411 AN: 10552

Middle Eastern (MID) AF: 0.559 AC: 162 AN: 290

European-Non Finnish (NFE) AF: 0.441 AC: 29967 AN: 67948

Other (OTH) AF: 0.423 AC: 892 AN: 2110

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	0.58
DANN	Benign	0.79
PhyloP100		-0.45

Splicing

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

Other links and lift over

dbSNP: rs502419; hg19: chr11-59866175;