rs1441585

Variant names:

• chr11-60088238-T-C
• rs1441585
• ENST00000524868.1:c.-440T>C

Variant summary

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

The ENST00000524868.1(MS4A2):​c.-440T>C variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0705 in 161,544 control chromosomes in the GnomAD database, including 847 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 0.073 (843 hom., cov: 32)
  • Exomes 𝑓: 0.024 (4 hom.)
• Consequence: MS4A2 ENST00000524868.1 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.04
• Publications: 13 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.179 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000524868.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MS4A2	ENST00000524868.1	TSL:4	c.-440T>C		upstream_gene	N/A	ENSP00000433311.1

Frequencies

GnomAD3 genomes AF: 0.0733 AC: 11144 AN: 152118 Hom.: 841 Cov.: 32

Gnomad AFR AF: 0.183

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0349

Gnomad ASJ AF: 0.0801

Gnomad EAS AF: 0.170

Gnomad SAS AF: 0.0489

Gnomad FIN AF: 0.00123

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0216

Gnomad OTH AF: 0.0636

GnomAD4 exome AF: 0.0244 AC: 227 AN: 9308 Hom.: 4 Cov.: 0 AF XY: 0.0276 AC XY: 136 AN XY: 4920

African (AFR) AF: 0.205 AC: 9 AN: 44

American (AMR) AF: 0.0249 AC: 36 AN: 1448

Ashkenazi Jewish (ASJ) AF: 0.0745 AC: 7 AN: 94

East Asian (EAS) AF: 0.101 AC: 32 AN: 318

South Asian (SAS) AF: 0.0444 AC: 36 AN: 810

European-Finnish (FIN) AF: 0.00505 AC: 1 AN: 198

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 12

European-Non Finnish (NFE) AF: 0.0166 AC: 99 AN: 5976

Other (OTH) AF: 0.0172 AC: 7 AN: 408

GnomAD4 genome AF: 0.0733 AC: 11155 AN: 152236 Hom.: 843 Cov.: 32 AF XY: 0.0713 AC XY: 5310 AN XY: 74434

African (AFR) AF: 0.183 AC: 7594 AN: 41516

American (AMR) AF: 0.0348 AC: 533 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0801 AC: 278 AN: 3470

East Asian (EAS) AF: 0.170 AC: 884 AN: 5188

South Asian (SAS) AF: 0.0485 AC: 234 AN: 4826

European-Finnish (FIN) AF: 0.00123 AC: 13 AN: 10602

Middle Eastern (MID) AF: 0.0714 AC: 21 AN: 294

European-Non Finnish (NFE) AF: 0.0216 AC: 1467 AN: 68016

Other (OTH) AF: 0.0620 AC: 131 AN: 2114

Alfa AF: 0.0404 Hom.: 1147

Bravo AF: 0.0808

Asia WGS AF: 0.117 AC: 407 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.59
DANN	Benign	0.68
PhyloP100		-1.0
PromoterAI		0.0088	Neutral

Splicing

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

Other links and lift over

dbSNP: rs1441585; hg19: chr11-59855711;