11-60095780-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000139.5(MS4A2):​c.*124C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0388 in 714,882 control chromosomes in the GnomAD database, including 1,142 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 0.052 ( 382 hom., cov: 32)
Exomes 𝑓: 0.035 ( 760 hom. )

Consequence

MS4A2
NM_000139.5 3_prime_UTR

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.742
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.85).
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.16 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
MS4A2NM_000139.5 linkuse as main transcriptc.*124C>T 3_prime_UTR_variant 7/7 ENST00000278888.8 NP_000130.1
MS4A2NM_001256916.2 linkuse as main transcriptc.*124C>T 3_prime_UTR_variant 6/6 NP_001243845.1
MS4A2XM_005273846.5 linkuse as main transcriptc.*124C>T 3_prime_UTR_variant 8/8 XP_005273903.1
MS4A2XM_011544850.3 linkuse as main transcriptc.*124C>T 3_prime_UTR_variant 8/8 XP_011543152.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
MS4A2ENST00000278888.8 linkuse as main transcriptc.*124C>T 3_prime_UTR_variant 7/71 NM_000139.5 ENSP00000278888 P1
MS4A2ENST00000617306.1 linkuse as main transcriptc.*124C>T 3_prime_UTR_variant 6/61 ENSP00000482594

Frequencies

GnomAD3 genomes
AF:
0.0522
AC:
7935
AN:
152026
Hom.:
380
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.111
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0280
Gnomad ASJ
AF:
0.0798
Gnomad EAS
AF:
0.169
Gnomad SAS
AF:
0.0485
Gnomad FIN
AF:
0.00123
Gnomad MID
AF:
0.0633
Gnomad NFE
AF:
0.0208
Gnomad OTH
AF:
0.0460
GnomAD4 exome
AF:
0.0351
AC:
19769
AN:
562738
Hom.:
760
Cov.:
5
AF XY:
0.0353
AC XY:
10716
AN XY:
303858
show subpopulations
Gnomad4 AFR exome
AF:
0.105
Gnomad4 AMR exome
AF:
0.0225
Gnomad4 ASJ exome
AF:
0.0732
Gnomad4 EAS exome
AF:
0.158
Gnomad4 SAS exome
AF:
0.0413
Gnomad4 FIN exome
AF:
0.00234
Gnomad4 NFE exome
AF:
0.0210
Gnomad4 OTH exome
AF:
0.0446
GnomAD4 genome
AF:
0.0522
AC:
7939
AN:
152144
Hom.:
382
Cov.:
32
AF XY:
0.0512
AC XY:
3808
AN XY:
74384
show subpopulations
Gnomad4 AFR
AF:
0.111
Gnomad4 AMR
AF:
0.0279
Gnomad4 ASJ
AF:
0.0798
Gnomad4 EAS
AF:
0.169
Gnomad4 SAS
AF:
0.0481
Gnomad4 FIN
AF:
0.00123
Gnomad4 NFE
AF:
0.0208
Gnomad4 OTH
AF:
0.0446
Alfa
AF:
0.0299
Hom.:
262
Bravo
AF:
0.0569
Asia WGS
AF:
0.113
AC:
391
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.85
CADD
Benign
2.3
DANN
Benign
0.39

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs512555; hg19: chr11-59863253; API