rs662196

Variant names:

• chr11-60175284-C-T
• rs662196
• NM_022349.4:c.549+118G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 25 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022349.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MS4A6A	NM_022349.4	MANE Select	c.549+118G>A		intron	N/A	NP_071744.2
	MS4A6A	NM_001330275.1		c.633+118G>A		intron	N/A	NP_001317204.1	E9PSA9
	MS4A6A	NM_001247999.2		c.633+118G>A		intron	N/A	NP_001234928.1	Q9H2W1-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MS4A6A	ENST00000528851.6	TSL:1 MANE Select	c.549+118G>A		intron	N/A	ENSP00000431901.1	Q9H2W1-2
	MS4A6A	ENST00000420732.6	TSL:1	c.445+222G>A		intron	N/A	ENSP00000392921.2	Q9H2W1-3
	MS4A6A	ENST00000529054.5	TSL:5	c.633+118G>A		intron	N/A	ENSP00000435844.1	E9PSA9

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

African (AFR) AF: 0.509 AC: 7929 AN: 15586

American (AMR) AF: 0.706 AC: 15330 AN: 21708

Ashkenazi Jewish (ASJ) AF: 0.517 AC: 7921 AN: 15316

East Asian (EAS) AF: 0.686 AC: 21796 AN: 31788

South Asian (SAS) AF: 0.434 AC: 21343 AN: 49152

European-Finnish (FIN) AF: 0.688 AC: 22351 AN: 32478

Middle Eastern (MID) AF: 0.462 AC: 1136 AN: 2460

European-Non Finnish (NFE) AF: 0.568 AC: 238627 AN: 420412

Other (OTH) AF: 0.557 AC: 17557 AN: 31506

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

African (AFR) AF: 0.507 AC: 20970 AN: 41394

American (AMR) AF: 0.648 AC: 9897 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.528 AC: 1832 AN: 3470

East Asian (EAS) AF: 0.635 AC: 3278 AN: 5164

South Asian (SAS) AF: 0.428 AC: 2054 AN: 4804

European-Finnish (FIN) AF: 0.709 AC: 7482 AN: 10546

Middle Eastern (MID) AF: 0.429 AC: 126 AN: 294

European-Non Finnish (NFE) AF: 0.572 AC: 38866 AN: 67976

Other (OTH) AF: 0.540 AC: 1139 AN: 2110

Alfa AF: 0.560 Hom.: 15399

Bravo AF: 0.563

Asia WGS AF: 0.523 AC: 1816 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.27
DANN	Benign	0.36
PhyloP100		-0.92
Mutation Taster		=100/0	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: rs662196; hg19: chr11-59942757; COSMIC: COSV60618786; COSMIC: COSV60618786;