chr11-60095631-A-G

Variant names:

• chr11-60095631-A-G
• rs569108
• NM_000139.5:c.710A>G

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_000139.5(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. 13/21 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 NM_000139.5 missense
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 3.59
• Publications: 87 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: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000139.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MS4A2	NM_000139.5	MANE Select	c.710A>G	p.Glu237Gly	missense	Exon 7 of 7	NP_000130.1
	MS4A2	NM_001256916.2		c.575A>G	p.Glu192Gly	missense	Exon 6 of 6	NP_001243845.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MS4A2	ENST00000278888.8	TSL:1 MANE Select	c.710A>G	p.Glu237Gly	missense	Exon 7 of 7	ENSP00000278888.3
	MS4A2	ENST00000617306.1	TSL:1	c.575A>G	p.Glu192Gly	missense	Exon 6 of 6	ENSP00000482594.1

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

GnomAD2 exomes AF: 0.0470 AC: 11814 AN: 251444 AF XY: 0.0441

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 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

African (AFR) AF: 0.185 AC: 6162 AN: 33254

American (AMR) AF: 0.0250 AC: 1119 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.0745 AC: 1944 AN: 26078

East Asian (EAS) AF: 0.162 AC: 6424 AN: 39644

South Asian (SAS) AF: 0.0425 AC: 3661 AN: 86174

European-Finnish (FIN) AF: 0.00234 AC: 125 AN: 53412

Middle Eastern (MID) AF: 0.0459 AC: 264 AN: 5752

European-Non Finnish (NFE) AF: 0.0214 AC: 23725 AN: 1107372

Other (OTH) AF: 0.0489 AC: 2943 AN: 60190

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

African (AFR) AF: 0.182 AC: 7566 AN: 41522

American (AMR) AF: 0.0350 AC: 536 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0801 AC: 278 AN: 3470

East Asian (EAS) AF: 0.170 AC: 880 AN: 5186

South Asian (SAS) AF: 0.0476 AC: 230 AN: 4828

European-Finnish (FIN) AF: 0.00122 AC: 13 AN: 10630

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.0212 AC: 1443 AN: 68012

Other (OTH) AF: 0.0617 AC: 130 AN: 2108

Alfa AF: 0.0428 Hom.: 1417

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 - MYOC POLYMORPHISM Benign:1

Sep 01, 2001

OMIM

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: literature only

Computational scores

Source: dbNSFP v4.9

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
MetaRNN	Benign	0.00092	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.5	L
PhyloP100		3.6
PrimateAI	Benign	0.34	T
PROVEAN	Uncertain	-3.8	D
REVEL	Benign	0.12
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.014	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
Mutation Taster		=94/6	polymorphism (auto)

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