rs512555

Variant names:

• chr11-60095780-C-A
• rs512555
• NM_000139.5:c.*124C>A

Your query was ambiguous. Multiple possible variants found:

• chr11-60095780-C-A
• chr11-60095780-C-G
• chr11-60095780-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_000139.5(MS4A2):​c.*124C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000355 in 562,876 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000036 (0 hom.)
• Consequence: MS4A2 NM_000139.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.742
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MS4A2	NM_000139.5	c.*124C>A		3_prime_UTR_variant	Exon 7 of 7	ENST00000278888.8	NP_000130.1
MS4A2	NM_001256916.2	c.*124C>A		3_prime_UTR_variant	Exon 6 of 6		NP_001243845.1
MS4A2	XM_005273846.5	c.*124C>A		3_prime_UTR_variant	Exon 8 of 8		XP_005273903.1
MS4A2	XM_011544850.3	c.*124C>A		3_prime_UTR_variant	Exon 8 of 8		XP_011543152.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MS4A2	ENST00000278888.8	c.*124C>A		3_prime_UTR_variant	Exon 7 of 7	1	NM_000139.5	ENSP00000278888.3
MS4A2	ENST00000617306.1	c.*124C>A		3_prime_UTR_variant	Exon 6 of 6	1		ENSP00000482594.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000355 AC: 2 AN: 562876 Hom.: 0 Cov.: 5 AF XY: 0.00000329 AC XY: 1 AN XY: 303930

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 15400

American (AMR) AF: 0.00 AC: 0 AN: 33564

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19610

East Asian (EAS) AF: 0.00 AC: 0 AN: 31946

South Asian (SAS) AF: 0.0000163 AC: 1 AN: 61310

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 44866

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4016

European-Non Finnish (NFE) AF: 0.00000311 AC: 1 AN: 321664

Other (OTH) AF: 0.00 AC: 0 AN: 30500

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.00666416), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.74
DANN	Benign	0.42
PhyloP100		-0.74

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

Other links and lift over

dbSNP: rs512555; hg19: chr11-59863253;