rs7232

Positions:

• chr11-60173126-T-A

Variant summary

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

The ENST00000528851.6(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. 12/16 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.27 (6919 hom., cov: 32)
  • Exomes 𝑓: 0.36 (98051 hom.)
• Consequence: MS4A6A ENST00000528851.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.30

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 (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/exons	MANE	Protein	UniProt
MS4A6A	NM_022349.4	c.553A>T	p.Thr185Ser	missense_variant	6/6	ENST00000528851.6	NP_071744.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MS4A6A	ENST00000528851.6	c.553A>T	p.Thr185Ser	missense_variant	6/6	1	NM_022349.4	ENSP00000431901

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

GnomAD3 exomes AF: 0.308 AC: 77415 AN: 251080 Hom.: 13945 AF XY: 0.327 AC XY: 44393 AN XY: 135678

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 SAS exome AF: 0.456

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

Gnomad4 AFR exome AF: 0.0844

Gnomad4 AMR exome AF: 0.188

Gnomad4 ASJ exome AF: 0.383

Gnomad4 EAS exome AF: 0.0567

Gnomad4 SAS exome AF: 0.454

Gnomad4 FIN exome AF: 0.292

Gnomad4 NFE exome AF: 0.378

Gnomad4 OTH exome AF: 0.348

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

Gnomad4 AFR AF: 0.0927

Gnomad4 AMR AF: 0.255

Gnomad4 ASJ AF: 0.365

Gnomad4 EAS AF: 0.0706

Gnomad4 SAS AF: 0.449

Gnomad4 FIN AF: 0.279

Gnomad4 NFE AF: 0.378

Gnomad4 OTH AF: 0.321

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
MutationTaster	Benign	1.0	P;P;P;P;P;P;P;P
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

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: rs7232; hg19: chr11-59940599; COSMIC: COSV60619240; COSMIC: COSV60619240;