XM_005273846.5:c.-647C>T

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.

Variant Effect in Transcripts

 

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	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 v4.9

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;