11-60091239-A-T

Position:

• chr11-60091239-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000139.5(MS4A2):​c.321+769A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.419 in 152,106 control chromosomes in the GnomAD database, including 13,554 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 0.42 (13554 hom., cov: 31)
• Consequence: MS4A2 NM_000139.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.15

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.532 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MS4A2	NM_000139.5	c.321+769A>T		intron_variant		ENST00000278888.8	NP_000130.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MS4A2	ENST00000278888.8	c.321+769A>T		intron_variant		1	NM_000139.5	ENSP00000278888.3
MS4A2	ENST00000617306.1	c.186+1418A>T		intron_variant		1		ENSP00000482594.1
MS4A2	ENST00000440896.2	n.423+769A>T		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.418 AC: 63601 AN: 151988 Hom.: 13536 Cov.: 31

Gnomad AFR AF: 0.414

Gnomad AMI AF: 0.427

Gnomad AMR AF: 0.349

Gnomad ASJ AF: 0.461

Gnomad EAS AF: 0.377

Gnomad SAS AF: 0.549

Gnomad FIN AF: 0.323

Gnomad MID AF: 0.582

Gnomad NFE AF: 0.442

Gnomad OTH AF: 0.448

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

GnomAD4 genome AF: 0.419 AC: 63660 AN: 152106 Hom.: 13554 Cov.: 31 AF XY: 0.414 AC XY: 30790 AN XY: 74380

Gnomad4 AFR AF: 0.414

Gnomad4 AMR AF: 0.349

Gnomad4 ASJ AF: 0.461

Gnomad4 EAS AF: 0.377

Gnomad4 SAS AF: 0.549

Gnomad4 FIN AF: 0.323

Gnomad4 NFE AF: 0.442

Gnomad4 OTH AF: 0.446

Alfa AF: 0.416 Hom.: 1650

Bravo AF: 0.416

Asia WGS AF: 0.470 AC: 1634 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.17
DANN	Benign	0.28

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs556917; hg19: chr11-59858712;