11-60092705-G-T

Variant summary

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

The NM_000139.5(MS4A2):c.322-87G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.435 in 1,207,896 control chromosomes in the GnomAD database, including 117,072 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 0.39 (12019 hom., cov: 32)
  • Exomes 𝑓: 0.44 (105053 hom.)
• Consequence: MS4A2 NM_000139.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.865

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=-0.97).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.532 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MS4A2	NM_000139.5	c.322-87G>T		intron_variant		ENST00000278888.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MS4A2	ENST00000278888.8	c.322-87G>T		intron_variant		1	NM_000139.5	P1
MS4A2	ENST00000617306.1	c.187-87G>T		intron_variant		1
MS4A2	ENST00000440896.2	n.424-87G>T		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.392 AC: 59516 AN: 151866 Hom.: 12012 Cov.: 32

Gnomad AFR AF: 0.322

Gnomad AMI AF: 0.427

Gnomad AMR AF: 0.339

Gnomad ASJ AF: 0.461

Gnomad EAS AF: 0.377

Gnomad SAS AF: 0.549

Gnomad FIN AF: 0.323

Gnomad MID AF: 0.563

Gnomad NFE AF: 0.441

Gnomad OTH AF: 0.428

GnomAD4 exome AF: 0.442 AC: 466369 AN: 1055912 Hom.: 105053 AF XY: 0.446 AC XY: 240171 AN XY: 538224

Gnomad4 AFR exome AF: 0.321

Gnomad4 AMR exome AF: 0.264

Gnomad4 ASJ exome AF: 0.478

Gnomad4 EAS exome AF: 0.336

Gnomad4 SAS exome AF: 0.540

Gnomad4 FIN exome AF: 0.334

Gnomad4 NFE exome AF: 0.455

Gnomad4 OTH exome AF: 0.450

GnomAD4 genome AF: 0.392 AC: 59550 AN: 151984 Hom.: 12019 Cov.: 32 AF XY: 0.388 AC XY: 28831 AN XY: 74298

Gnomad4 AFR AF: 0.322

Gnomad4 AMR AF: 0.338

Gnomad4 ASJ AF: 0.461

Gnomad4 EAS AF: 0.377

Gnomad4 SAS AF: 0.549

Gnomad4 FIN AF: 0.323

Gnomad4 NFE AF: 0.441

Gnomad4 OTH AF: 0.427

Alfa AF: 0.428 Hom.: 11898

Bravo AF: 0.385

Asia WGS AF: 0.461 AC: 1604 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
Cadd	Benign	3.2
Dann	Benign	0.14

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: rs502581; hg19: chr11-59860178; COSMIC: COSV54012055; COSMIC: COSV54012055;