11-60095631-A-G

Position:

• chr11-60095631-A-G

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The ENST00000278888.8(MS4A2):​c.710A>G​(p.Glu237Gly) variant causes a missense change. The variant allele was found at a frequency of 0.0357 in 1,608,858 control chromosomes in the GnomAD database, including 2,535 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.073 (831 hom., cov: 32)
  • Exomes 𝑓: 0.032 (1704 hom.)
• Consequence: MS4A2 ENST00000278888.8 missense
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 3.59

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=9.176135E-4).
• BP6: Variant 11-60095631-A-G is Benign according to our data. Variant chr11-60095631-A-G is described in ClinVar as [Benign]. Clinvar id is 14807.Status of the report is no_assertion_criteria_provided, 0 stars.
• 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/exons	MANE	Protein	UniProt
MS4A2	NM_000139.5	c.710A>G	p.Glu237Gly	missense_variant	7/7	ENST00000278888.8	NP_000130.1
MS4A2	NM_001256916.2	c.575A>G	p.Glu192Gly	missense_variant	6/6		NP_001243845.1
MS4A2	XM_005273846.5	c.731A>G	p.Glu244Gly	missense_variant	8/8		XP_005273903.1
MS4A2	XM_011544850.3	c.710A>G	p.Glu237Gly	missense_variant	8/8		XP_011543152.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MS4A2	ENST00000278888.8	c.710A>G	p.Glu237Gly	missense_variant	7/7	1	NM_000139.5	ENSP00000278888	P1
MS4A2	ENST00000617306.1	c.575A>G	p.Glu192Gly	missense_variant	6/6	1		ENSP00000482594

Frequencies

GnomAD3 genomes AF: 0.0729 AC: 11084 AN: 152148 Hom.: 829 Cov.: 32

Gnomad AFR AF: 0.182

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0351

Gnomad ASJ AF: 0.0801

Gnomad EAS AF: 0.170

Gnomad SAS AF: 0.0480

Gnomad FIN AF: 0.00122

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0212

Gnomad OTH AF: 0.0633

GnomAD3 exomes AF: 0.0470 AC: 11814 AN: 251444 Hom.: 672 AF XY: 0.0441 AC XY: 5994 AN XY: 135900

Gnomad AFR exome AF: 0.182

Gnomad AMR exome AF: 0.0240

Gnomad ASJ exome AF: 0.0757

Gnomad EAS exome AF: 0.176

Gnomad SAS exome AF: 0.0454

Gnomad FIN exome AF: 0.00129

Gnomad NFE exome AF: 0.0208

Gnomad OTH exome AF: 0.0391

GnomAD4 exome AF: 0.0318 AC: 46367 AN: 1456592 Hom.: 1704 Cov.: 28 AF XY: 0.0316 AC XY: 22928 AN XY: 725096

Gnomad4 AFR exome AF: 0.185

Gnomad4 AMR exome AF: 0.0250

Gnomad4 ASJ exome AF: 0.0745

Gnomad4 EAS exome AF: 0.162

Gnomad4 SAS exome AF: 0.0425

Gnomad4 FIN exome AF: 0.00234

Gnomad4 NFE exome AF: 0.0214

Gnomad4 OTH exome AF: 0.0489

GnomAD4 genome AF: 0.0729 AC: 11096 AN: 152266 Hom.: 831 Cov.: 32 AF XY: 0.0711 AC XY: 5292 AN XY: 74452

Gnomad4 AFR AF: 0.182

Gnomad4 AMR AF: 0.0350

Gnomad4 ASJ AF: 0.0801

Gnomad4 EAS AF: 0.170

Gnomad4 SAS AF: 0.0476

Gnomad4 FIN AF: 0.00122

Gnomad4 NFE AF: 0.0212

Gnomad4 OTH AF: 0.0617

Alfa AF: 0.0379 Hom.: 544

Bravo AF: 0.0805

TwinsUK AF: 0.0197 AC: 73

ALSPAC AF: 0.0200 AC: 77

ESP6500AA AF: 0.171 AC: 752

ESP6500EA AF: 0.0231 AC: 198

ExAC AF: 0.0484 AC: 5881

Asia WGS AF: 0.116 AC: 402 AN: 3478

EpiCase AF: 0.0255

EpiControl AF: 0.0256

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

RECLASSIFIED - POLYMORPHISM Benign:1

Benign, no assertion criteria provided

literature only

OMIM

Sep 01, 2001

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.093
BayesDel_addAF	Benign	-0.62	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	19
DANN	Uncertain	1.0
DEOGEN2	Benign	0.34	T;.
Eigen	Benign	-0.069
Eigen_PC	Benign	-0.19
FATHMM_MKL	Benign	0.16	N
LIST_S2	Benign	0.46	T;T
MetaRNN	Benign	0.00092	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.5	L;.
MutationTaster	Benign	1.0	P
PrimateAI	Benign	0.34	T
PROVEAN	Uncertain	-3.8	D;.
REVEL	Benign	0.12
Sift	Uncertain	0.0020	D;.
Sift4G	Uncertain	0.014	D;D
Polyphen		0.95	P;.
Vest4		0.075
MPC		0.083
ClinPred		0.060	T
GERP RS		4.8
Varity_R		0.14
gMVP		0.40

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: rs569108; hg19: chr11-59863104; COSMIC: COSV54011661; COSMIC: COSV54011661;