11-60088555-T-C

Variant names:

• chr11-60088555-T-C
• rs1441586
• ENST00000524868.1:c.-123T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000524868.1(MS4A2):​c.-123T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.438 in 1,342,428 control chromosomes in the GnomAD database, including 130,268 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 0.44 (14930 hom., cov: 31)
  • Exomes 𝑓: 0.44 (115338 hom.)
• Consequence: MS4A2 ENST00000524868.1 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.703
• Publications: 49 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=-0.9).
• 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.-211T>C		upstream_gene_variant		ENST00000278888.8	NP_000130.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MS4A2	ENST00000524868.1	c.-123T>C		5_prime_UTR_variant	Exon 1 of 3	4		ENSP00000433311.1
MS4A2	ENST00000278888.8	c.-211T>C		upstream_gene_variant		1	NM_000139.5	ENSP00000278888.3
MS4A2	ENST00000617306.1	c.-211T>C		upstream_gene_variant		1		ENSP00000482594.1
MS4A2	ENST00000440896.2	n.-109T>C		upstream_gene_variant		1

Frequencies

GnomAD3 genomes AF: 0.439 AC: 66693 AN: 151890 Hom.: 14901 Cov.: 31

Gnomad AFR AF: 0.498

Gnomad AMI AF: 0.371

Gnomad AMR AF: 0.352

Gnomad ASJ AF: 0.463

Gnomad EAS AF: 0.377

Gnomad SAS AF: 0.546

Gnomad FIN AF: 0.322

Gnomad MID AF: 0.599

Gnomad NFE AF: 0.437

Gnomad OTH AF: 0.459

GnomAD4 exome AF: 0.437 AC: 520752 AN: 1190420 Hom.: 115338 Cov.: 16 AF XY: 0.440 AC XY: 254612 AN XY: 578722

African (AFR) AF: 0.501 AC: 13160 AN: 26288

American (AMR) AF: 0.305 AC: 5482 AN: 17986

Ashkenazi Jewish (ASJ) AF: 0.475 AC: 8102 AN: 17048

East Asian (EAS) AF: 0.338 AC: 10613 AN: 31364

South Asian (SAS) AF: 0.539 AC: 29741 AN: 55140

European-Finnish (FIN) AF: 0.340 AC: 9684 AN: 28504

Middle Eastern (MID) AF: 0.535 AC: 1783 AN: 3332

European-Non Finnish (NFE) AF: 0.437 AC: 419847 AN: 961846

Other (OTH) AF: 0.457 AC: 22340 AN: 48912

GnomAD4 genome AF: 0.439 AC: 66764 AN: 152008 Hom.: 14930 Cov.: 31 AF XY: 0.434 AC XY: 32219 AN XY: 74300

African (AFR) AF: 0.498 AC: 20638 AN: 41418

American (AMR) AF: 0.351 AC: 5364 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.463 AC: 1606 AN: 3470

East Asian (EAS) AF: 0.376 AC: 1949 AN: 5178

South Asian (SAS) AF: 0.547 AC: 2636 AN: 4820

European-Finnish (FIN) AF: 0.322 AC: 3404 AN: 10570

Middle Eastern (MID) AF: 0.596 AC: 174 AN: 292

European-Non Finnish (NFE) AF: 0.437 AC: 29688 AN: 67966

Other (OTH) AF: 0.457 AC: 968 AN: 2116

Alfa AF: 0.440 Hom.: 40515

Bravo AF: 0.440

Asia WGS AF: 0.478 AC: 1663 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.1
DANN	Benign	0.63
PhyloP100		-0.70
PromoterAI		-0.0065	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs1441586; hg19: chr11-59856028;