rs12453

Positions:

• chr11-60178272-T-C
• chr11-60178272-T-G

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_022349.4(MS4A6A):​c.327A>G​(p.Leu109Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.384 in 1,609,884 control chromosomes in the GnomAD database, including 123,466 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 0.33 (8828 hom., cov: 31)
  • Exomes 𝑓: 0.39 (114638 hom.)
• Consequence: MS4A6A NM_022349.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.549

Genes affected

MS4A6A (HGNC:13375): (membrane spanning 4-domains A6A) This gene encodes 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. The gene encoding this protein is localized to 11q12.1, among a cluster of family members. Alternative splicing of this gene results in several transcript variants that encode different protein isoforms. [provided by RefSeq, Oct 2011]

MS4A6A (HGNC:):

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP7: Synonymous conserved (PhyloP=-0.549 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.486 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MS4A6A	NM_022349.4	c.327A>G	p.Leu109Leu	synonymous_variant	4/6	ENST00000528851.6	NP_071744.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MS4A6A	ENST00000528851.6	c.327A>G	p.Leu109Leu	synonymous_variant	4/6	1	NM_022349.4	ENSP00000431901.1

Frequencies

GnomAD3 genomes AF: 0.327 AC: 49685 AN: 151922 Hom.: 8824 Cov.: 31

Gnomad AFR AF: 0.205

Gnomad AMI AF: 0.427

Gnomad AMR AF: 0.300

Gnomad ASJ AF: 0.382

Gnomad EAS AF: 0.219

Gnomad SAS AF: 0.503

Gnomad FIN AF: 0.289

Gnomad MID AF: 0.472

Gnomad NFE AF: 0.403

Gnomad OTH AF: 0.369

GnomAD3 exomes AF: 0.354 AC: 88762 AN: 250862 Hom.: 17076 AF XY: 0.371 AC XY: 50272 AN XY: 135630

Gnomad AFR exome AF: 0.199

Gnomad AMR exome AF: 0.218

Gnomad ASJ exome AF: 0.400

Gnomad EAS exome AF: 0.210

Gnomad SAS exome AF: 0.501

Gnomad FIN exome AF: 0.299

Gnomad NFE exome AF: 0.406

Gnomad OTH exome AF: 0.382

GnomAD4 exome AF: 0.390 AC: 568807 AN: 1457844 Hom.: 114638 Cov.: 32 AF XY: 0.395 AC XY: 286511 AN XY: 725380

Gnomad4 AFR exome AF: 0.196

Gnomad4 AMR exome AF: 0.230

Gnomad4 ASJ exome AF: 0.402

Gnomad4 EAS exome AF: 0.180

Gnomad4 SAS exome AF: 0.499

Gnomad4 FIN exome AF: 0.303

Gnomad4 NFE exome AF: 0.405

Gnomad4 OTH exome AF: 0.388

GnomAD4 genome AF: 0.327 AC: 49710 AN: 152040 Hom.: 8828 Cov.: 31 AF XY: 0.325 AC XY: 24190 AN XY: 74336

Gnomad4 AFR AF: 0.205

Gnomad4 AMR AF: 0.299

Gnomad4 ASJ AF: 0.382

Gnomad4 EAS AF: 0.218

Gnomad4 SAS AF: 0.503

Gnomad4 FIN AF: 0.289

Gnomad4 NFE AF: 0.403

Gnomad4 OTH AF: 0.370

Alfa AF: 0.387 Hom.: 22801

Bravo AF: 0.320

Asia WGS AF: 0.345 AC: 1199 AN: 3478

EpiCase AF: 0.428

EpiControl AF: 0.422

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.52
DANN	Benign	0.47

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs12453; hg19: chr11-59945745; COSMIC: COSV60617558; COSMIC: COSV60617558;