rs574700

Variant names:

• chr11-60088010-C-T
• rs574700
• XM_005273846.5:c.-647C>T

Variant summary

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

The XM_005273846.5(MS4A2):​c.-647C>T variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0856 in 152,214 control chromosomes in the GnomAD database, including 1,227 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 0.086 (1227 hom., cov: 32)
• Consequence: MS4A2 XM_005273846.5 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0330
• Publications: 18 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 (AFR) allele frequency at 95% confidence interval = 0.223 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MS4A2	XM_005273846.5	c.-647C>T		upstream_gene_variant			XP_005273903.1
MS4A2	XM_011544850.3	c.-331C>T		upstream_gene_variant			XP_011543152.1
MS4A2	XM_017017362.2	c.-647C>T		upstream_gene_variant			XP_016872851.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD3 genomes AF: 0.0855 AC: 12999 AN: 152096 Hom.: 1221 Cov.: 32

Gnomad AFR AF: 0.227

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0402

Gnomad ASJ AF: 0.0791

Gnomad EAS AF: 0.166

Gnomad SAS AF: 0.0460

Gnomad FIN AF: 0.00113

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.0213

Gnomad OTH AF: 0.0697

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

GnomAD4 genome AF: 0.0856 AC: 13026 AN: 152214 Hom.: 1227 Cov.: 32 AF XY: 0.0826 AC XY: 6149 AN XY: 74438

African (AFR) AF: 0.227 AC: 9435 AN: 41506

American (AMR) AF: 0.0402 AC: 615 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0791 AC: 274 AN: 3466

East Asian (EAS) AF: 0.166 AC: 860 AN: 5178

South Asian (SAS) AF: 0.0456 AC: 220 AN: 4826

European-Finnish (FIN) AF: 0.00113 AC: 12 AN: 10614

Middle Eastern (MID) AF: 0.0646 AC: 19 AN: 294

European-Non Finnish (NFE) AF: 0.0213 AC: 1447 AN: 68020

Other (OTH) AF: 0.0681 AC: 144 AN: 2116

Alfa AF: 0.0427 Hom.: 1641

Bravo AF: 0.0945

Asia WGS AF: 0.119 AC: 413 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	2.5
DANN	Benign	0.23
PhyloP100		-0.033
PromoterAI		-0.0080	Neutral

Splicing

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

Other links and lift over

dbSNP: rs574700; hg19: chr11-59855483;