chr11-60092705-G-T

Variant names:

• chr11-60092705-G-T
• rs502581
• NM_000139.5:c.322-87G>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 29 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=-0.97).
• 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 rank	MANE	Protein	UniProt
MS4A2	NM_000139.5	c.322-87G>T		intron_variant	Intron 3 of 6	ENST00000278888.8	NP_000130.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MS4A2	ENST00000278888.8	c.322-87G>T		intron_variant	Intron 3 of 6	1	NM_000139.5	ENSP00000278888.3
MS4A2	ENST00000617306.1	c.187-87G>T		intron_variant	Intron 2 of 5	1		ENSP00000482594.1
MS4A2	ENST00000440896.2	n.424-87G>T		intron_variant	Intron 3 of 4	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

African (AFR) AF: 0.321 AC: 8018 AN: 24944

American (AMR) AF: 0.264 AC: 9827 AN: 37200

Ashkenazi Jewish (ASJ) AF: 0.478 AC: 11144 AN: 23306

East Asian (EAS) AF: 0.336 AC: 12169 AN: 36220

South Asian (SAS) AF: 0.540 AC: 39910 AN: 73940

European-Finnish (FIN) AF: 0.334 AC: 16958 AN: 50786

Middle Eastern (MID) AF: 0.544 AC: 2091 AN: 3844

European-Non Finnish (NFE) AF: 0.455 AC: 345299 AN: 759074

Other (OTH) AF: 0.450 AC: 20953 AN: 46598

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

African (AFR) AF: 0.322 AC: 13339 AN: 41424

American (AMR) AF: 0.338 AC: 5172 AN: 15286

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

East Asian (EAS) AF: 0.377 AC: 1948 AN: 5172

South Asian (SAS) AF: 0.549 AC: 2645 AN: 4818

European-Finnish (FIN) AF: 0.323 AC: 3409 AN: 10548

Middle Eastern (MID) AF: 0.561 AC: 165 AN: 294

European-Non Finnish (NFE) AF: 0.441 AC: 29988 AN: 67960

Other (OTH) AF: 0.427 AC: 900 AN: 2110

Alfa AF: 0.426 Hom.: 13544

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
PhyloP100		0.86
Mutation Taster		=100/0	polymorphism (auto)

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