Genetic Variant MS4A6A:c.282+52G>A (chr11-60179779-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.372

Variant links:

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]

MS4A6A links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MS4A6A	NM_022349.4 link	c.282+52G>A		intron_variant	Intron 3 of 5	ENST00000528851.6	NP_071744.2	Q9H2W1-2A0A024R516

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MS4A6A	ENST00000528851.6 link	c.282+52G>A		intron_variant	Intron 3 of 5	1	NM_022349.4	ENSP00000431901.1		Q9H2W1-2

Frequencies

GnomAD3 genomes

AF:

0.568

AC:

86178

AN:

151754

Hom.:

24774

Cov.:

show subpopulations

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

GnomAD3 exomes

AF:

0.588

AC:

147236

AN:

250528

Hom.:

44449

AF XY:

0.575

AC XY:

77866

AN XY:

135370

show subpopulations

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 SAS exome

AF:

0.433

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.:

AF XY:

0.566

AC XY:

409516

AN XY:

723786

show subpopulations

Gnomad4 AFR exome

AF:

0.510

Gnomad4 AMR exome

AF:

0.737

Gnomad4 ASJ exome

AF:

0.517

Gnomad4 EAS exome

AF:

0.678

Gnomad4 SAS exome

AF:

0.435

Gnomad4 FIN exome

AF:

0.695

Gnomad4 NFE exome

AF:

0.569

Gnomad4 OTH exome

AF:

0.552

GnomAD4 genome

AF:

0.568

AC:

86226

AN:

151872

Hom.:

24789

Cov.:

AF XY:

0.573

AC XY:

42535

AN XY:

74214

show subpopulations

Gnomad4 AFR

AF:

0.506

Gnomad4 AMR

AF:

0.651

Gnomad4 ASJ

AF:

0.529

Gnomad4 EAS

AF:

0.634

Gnomad4 SAS

AF:

0.429

Gnomad4 FIN

AF:

0.710

Gnomad4 NFE

AF:

0.573

Gnomad4 OTH

AF:

0.540

Alfa

AF:

0.557

Hom.:

15818

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 v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.77

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

LIST_S2

Benign

0.34

MetaRNN

Benign

0.0000024

MetaSVM

Benign

-1.0

PROVEAN

Benign

0.28

REVEL

Benign

0.066

Sift

Benign

0.083

Sift4G

Pathogenic

0.0

Vest4

0.065

ClinPred

0.0039

GERP RS

3.0

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over