rs7232

Variant names:

• chr11-60173126-T-A
• rs7232
• NM_022349.4:c.553A>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_022349.4(MS4A6A):​c.553A>T​(p.Thr185Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.349 in 1,610,750 control chromosomes in the GnomAD database, including 104,970 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/17 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.27 (6919 hom., cov: 32)
  • Exomes 𝑓: 0.36 (98051 hom.)
• Consequence: MS4A6A NM_022349.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.30
• Publications: 61 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=1.7395616E-4).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.433 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MS4A6A	NM_022349.4	c.553A>T	p.Thr185Ser	missense_variant	Exon 6 of 6	ENST00000528851.6	NP_071744.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MS4A6A	ENST00000528851.6	c.553A>T	p.Thr185Ser	missense_variant	Exon 6 of 6	1	NM_022349.4	ENSP00000431901.1

Frequencies

GnomAD3 genomes AF: 0.272 AC: 41186 AN: 151360 Hom.: 6920 Cov.: 32

Gnomad AFR AF: 0.0929

Gnomad AMI AF: 0.405

Gnomad AMR AF: 0.256

Gnomad ASJ AF: 0.365

Gnomad EAS AF: 0.0707

Gnomad SAS AF: 0.449

Gnomad FIN AF: 0.279

Gnomad MID AF: 0.415

Gnomad NFE AF: 0.378

Gnomad OTH AF: 0.320

GnomAD2 exomes AF: 0.308 AC: 77415 AN: 251080 AF XY: 0.327

Gnomad AFR exome AF: 0.0892

Gnomad AMR exome AF: 0.174

Gnomad ASJ exome AF: 0.381

Gnomad EAS exome AF: 0.0592

Gnomad FIN exome AF: 0.288

Gnomad NFE exome AF: 0.377

Gnomad OTH exome AF: 0.343

GnomAD4 exome AF: 0.357 AC: 520684 AN: 1459274 Hom.: 98051 Cov.: 34 AF XY: 0.361 AC XY: 262326 AN XY: 726034

African (AFR) AF: 0.0844 AC: 2823 AN: 33450

American (AMR) AF: 0.188 AC: 8405 AN: 44694

Ashkenazi Jewish (ASJ) AF: 0.383 AC: 9985 AN: 26094

East Asian (EAS) AF: 0.0567 AC: 2250 AN: 39666

South Asian (SAS) AF: 0.454 AC: 39134 AN: 86190

European-Finnish (FIN) AF: 0.292 AC: 15546 AN: 53312

Middle Eastern (MID) AF: 0.419 AC: 2412 AN: 5756

European-Non Finnish (NFE) AF: 0.378 AC: 419136 AN: 1109834

Other (OTH) AF: 0.348 AC: 20993 AN: 60278

GnomAD4 genome AF: 0.272 AC: 41188 AN: 151476 Hom.: 6919 Cov.: 32 AF XY: 0.270 AC XY: 19993 AN XY: 74000

African (AFR) AF: 0.0927 AC: 3822 AN: 41238

American (AMR) AF: 0.255 AC: 3887 AN: 15222

Ashkenazi Jewish (ASJ) AF: 0.365 AC: 1268 AN: 3470

East Asian (EAS) AF: 0.0706 AC: 363 AN: 5140

South Asian (SAS) AF: 0.449 AC: 2149 AN: 4788

European-Finnish (FIN) AF: 0.279 AC: 2918 AN: 10466

Middle Eastern (MID) AF: 0.422 AC: 124 AN: 294

European-Non Finnish (NFE) AF: 0.378 AC: 25611 AN: 67840

Other (OTH) AF: 0.321 AC: 679 AN: 2112

Alfa AF: 0.352 Hom.: 7674

Bravo AF: 0.259

TwinsUK AF: 0.384 AC: 1424

ALSPAC AF: 0.378 AC: 1458

ESP6500AA AF: 0.0972 AC: 428

ESP6500EA AF: 0.370 AC: 3180

ExAC AF: 0.313 AC: 37992

Asia WGS AF: 0.261 AC: 908 AN: 3478

EpiCase AF: 0.393

EpiControl AF: 0.388

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.59	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	0.68
DANN	Benign	0.80
Eigen	Benign	-0.97
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.056	N
LIST_S2	Benign	0.41	T;T
MetaRNN	Benign	0.00017	T;T
MetaSVM	Benign	-0.98	T
PhyloP100		-2.3
PROVEAN	Benign	-1.4	N;N
REVEL	Benign	0.0060
Sift	Uncertain	0.0060	D;T
Sift4G	Benign	0.19	T;T
Polyphen		0.10	B;.
Vest4		0.29
ClinPred		0.0086	T
GERP RS		-5.1
Varity_R		0.11
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: rs7232; hg19: chr11-59940599; COSMIC: COSV60619240; COSMIC: COSV60619240;