11-60179779-C-T

Variant names:

• chr11-60179779-C-T
• rs583791
• NM_022349.4:c.282+52G>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.282+52G>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 1,605,708 control chromosomes in the GnomAD database, including 264,380 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 (24789 hom., cov: 30)
  • Exomes 𝑓: 0.57 (239591 hom.)
• Consequence: MS4A6A NM_022349.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.372
• Publications: 37 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 (MetaRNN=2.3942785E-6).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.64 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.282+52G>A		intron	N/A	NP_071744.2
	MS4A6A	NM_001330275.1		c.366+52G>A		intron	N/A	NP_001317204.1	E9PSA9
	MS4A6A	NM_001247999.2		c.366+52G>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.282+52G>A		intron	N/A	ENSP00000431901.1	Q9H2W1-2
	MS4A6A	ENST00000420732.6	TSL:1	c.282+52G>A		intron	N/A	ENSP00000392921.2	Q9H2W1-3
	MS4A6A	ENST00000532169.5	TSL:2	c.334G>A	p.Ala112Thr	missense	Exon 4 of 4	ENSP00000431266.1	Q9H2W1-4

Frequencies

GnomAD3 genomes AF: 0.568 AC: 86178 AN: 151754 Hom.: 24774 Cov.: 30

Gnomad AFR AF: 0.507

Gnomad AMI AF: 0.565

Gnomad AMR AF: 0.650

Gnomad ASJ AF: 0.529

Gnomad EAS AF: 0.634

Gnomad SAS AF: 0.429

Gnomad FIN AF: 0.710

Gnomad MID AF: 0.427

Gnomad NFE AF: 0.573

Gnomad OTH AF: 0.540

GnomAD2 exomes AF: 0.588 AC: 147236 AN: 250528 AF XY: 0.575

Gnomad AFR exome AF: 0.509

Gnomad AMR exome AF: 0.750

Gnomad ASJ exome AF: 0.517

Gnomad EAS exome AF: 0.634

Gnomad FIN exome AF: 0.700

Gnomad NFE exome AF: 0.569

Gnomad OTH exome AF: 0.571

GnomAD4 exome AF: 0.571 AC: 829520 AN: 1453836 Hom.: 239591 Cov.: 31 AF XY: 0.566 AC XY: 409516 AN XY: 723786

African (AFR) AF: 0.510 AC: 16984 AN: 33312

American (AMR) AF: 0.737 AC: 32915 AN: 44662

Ashkenazi Jewish (ASJ) AF: 0.517 AC: 13476 AN: 26088

East Asian (EAS) AF: 0.678 AC: 26864 AN: 39646

South Asian (SAS) AF: 0.435 AC: 37473 AN: 86126

European-Finnish (FIN) AF: 0.695 AC: 37117 AN: 53398

Middle Eastern (MID) AF: 0.450 AC: 2593 AN: 5758

European-Non Finnish (NFE) AF: 0.569 AC: 628907 AN: 1104744

Other (OTH) AF: 0.552 AC: 33191 AN: 60102

GnomAD4 genome AF: 0.568 AC: 86226 AN: 151872 Hom.: 24789 Cov.: 30 AF XY: 0.573 AC XY: 42535 AN XY: 74214

African (AFR) AF: 0.506 AC: 20954 AN: 41382

American (AMR) AF: 0.651 AC: 9937 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.529 AC: 1834 AN: 3466

East Asian (EAS) AF: 0.634 AC: 3260 AN: 5138

South Asian (SAS) AF: 0.429 AC: 2065 AN: 4808

European-Finnish (FIN) AF: 0.710 AC: 7506 AN: 10570

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

European-Non Finnish (NFE) AF: 0.573 AC: 38890 AN: 67922

Other (OTH) AF: 0.540 AC: 1140 AN: 2110

Alfa AF: 0.553 Hom.: 19141

Bravo AF: 0.564

TwinsUK AF: 0.569 AC: 2111

ALSPAC AF: 0.559 AC: 2156

ESP6500AA AF: 0.491 AC: 859

ESP6500EA AF: 0.584 AC: 2321

ExAC AF: 0.579 AC: 70241

Asia WGS AF: 0.524 AC: 1821 AN: 3478

EpiCase AF: 0.541

EpiControl AF: 0.547

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.068
BayesDel_addAF	Benign	-0.77	T
BayesDel_noAF	Benign	-0.74
CADD	Benign	3.0
DANN	Uncertain	0.99
Eigen	Benign	-0.43
Eigen_PC	Benign	-0.58
FATHMM_MKL	Benign	0.053	N
LIST_S2	Benign	0.34	T
MetaRNN	Benign	0.0000024	T
MetaSVM	Benign	-1.0	T
PhyloP100		-0.37
PROVEAN	Benign	0.28	N
REVEL	Benign	0.066
Sift	Benign	0.083	T
Sift4G	Pathogenic	0.0	D
Vest4		0.065
ClinPred		0.0039	T
GERP RS		3.0
Mutation Taster		=98/2	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: rs583791; hg19: chr11-59947252;