Genetic Variant NM_022349.4:c.549+118G>A (chr11-60175284-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.916

Publications

24 publications found

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 was made for transcript

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MS4A6A	NM_022349.4 link	c.549+118G>A		intron_variant	Intron 5 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.549+118G>A		intron_variant	Intron 5 of 5	1	NM_022349.4	ENSP00000431901.1		Q9H2W1-2

Frequencies

GnomAD3 genomes

AF:

0.567

AC:

86110

AN:

151824

Hom.:

24714

Cov.:

show subpopulations

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

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

7436

14872

22308

29744

37180

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3826

7652

11478

15304

19130

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.567

AC:

86159

AN:

151936

Hom.:

24730

Cov.:

AF XY:

0.572

AC XY:

42493

AN XY:

74238

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1879

3759

5638

7518

9397

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

730

1460

2190

2920

3650

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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 v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.27

(source)

DANN

Benign

0.36

PhyloP100

-0.92

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over