rs1441585

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MS4A2	XM_005273846.5	c.-419T>C		upstream_gene_variant			XP_005273903.1
MS4A2	XM_011544850.3	c.-103T>C		upstream_gene_variant			XP_011543152.1
MS4A2	XM_017017362.2	c.-419T>C		upstream_gene_variant			XP_016872851.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MS4A2	ENST00000524868.1	c.-440T>C		upstream_gene_variant		4		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

Gnomad4 AFR exome AF: 0.205

Gnomad4 AMR exome AF: 0.0249

Gnomad4 ASJ exome AF: 0.0745

Gnomad4 EAS exome AF: 0.101

Gnomad4 SAS exome AF: 0.0444

Gnomad4 FIN exome AF: 0.00505

Gnomad4 NFE exome AF: 0.0166

Gnomad4 OTH exome AF: 0.0172

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

Gnomad4 AFR AF: 0.183

Gnomad4 AMR AF: 0.0348

Gnomad4 ASJ AF: 0.0801

Gnomad4 EAS AF: 0.170

Gnomad4 SAS AF: 0.0485

Gnomad4 FIN AF: 0.00123

Gnomad4 NFE AF: 0.0216

Gnomad4 OTH AF: 0.0620

Alfa AF: 0.0336 Hom.: 317

Bravo AF: 0.0808

Asia WGS AF: 0.117 AC: 407 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.59
DANN	Benign	0.68

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1441585; hg19: chr11-59855711;