rs662196

chr11-60175284-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_022349.4(MS4A6A):c.549+118G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.57 in 772,342 control chromosomes in the GnomAD database, including 127,461 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 0.57 (24730 hom., cov: 32)
  • Exomes 𝑓: 0.57 (102731 hom.)
• Consequence: MS4A6A NM_022349.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.916

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.638 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MS4A6A	NM_022349.4	c.549+118G>A		intron_variant		ENST00000528851.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MS4A6A	ENST00000528851.6	c.549+118G>A		intron_variant		1	NM_022349.4

Frequencies

GnomAD3 genomes AF: 0.567 AC: 86110 AN: 151824 Hom.: 24714 Cov.: 32

Gnomad AFR AF: 0.507

Gnomad AMI AF: 0.566

Gnomad AMR AF: 0.648

Gnomad ASJ AF: 0.528

Gnomad EAS AF: 0.634

Gnomad SAS AF: 0.427

Gnomad FIN AF: 0.709

Gnomad MID AF: 0.427

Gnomad NFE AF: 0.572

Gnomad OTH AF: 0.539

GnomAD4 exome AF: 0.571 AC: 353990 AN: 620406 Hom.: 102731 AF XY: 0.564 AC XY: 180826 AN XY: 320768

Gnomad4 AFR exome AF: 0.509

Gnomad4 AMR exome AF: 0.706

Gnomad4 ASJ exome AF: 0.517

Gnomad4 EAS exome AF: 0.686

Gnomad4 SAS exome AF: 0.434

Gnomad4 FIN exome AF: 0.688

Gnomad4 NFE exome AF: 0.568

Gnomad4 OTH exome AF: 0.557

GnomAD4 genome AF: 0.567 AC: 86159 AN: 151936 Hom.: 24730 Cov.: 32 AF XY: 0.572 AC XY: 42493 AN XY: 74238

Gnomad4 AFR AF: 0.507

Gnomad4 AMR AF: 0.648

Gnomad4 ASJ AF: 0.528

Gnomad4 EAS AF: 0.635

Gnomad4 SAS AF: 0.428

Gnomad4 FIN AF: 0.709

Gnomad4 NFE AF: 0.572

Gnomad4 OTH AF: 0.540

Alfa AF: 0.559 Hom.: 13993

Bravo AF: 0.563

Asia WGS AF: 0.523 AC: 1816 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	0.27
Dann	Benign	0.36

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: rs662196; hg19: chr11-59942757; COSMIC: COSV60618786; COSMIC: COSV60618786;