dbSNP rs2298585: MS4A3:c.615+44C>T (chr11-60069719-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_006138.5(MS4A3):c.615+44C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00936 in 1,435,424 control chromosomes in the GnomAD database, including 569 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 0.024 ( 124 hom., cov: 32)

Exomes 𝑓: 0.0077 ( 445 hom. )

Consequence

MS4A3
NM_006138.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.139

Publications

15 publications found

Variant links:

Genes affected

MS4A3 (HGNC:7317): (membrane spanning 4-domains A3) This gene encodes a member of the membrane-spanning 4A gene family. Members of this 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. This family member likely plays a role in signal transduction and may function as a subunit associated with receptor complexes. The gene encoding this protein is localized to 11q12, among a cluster of related family members. Alternative splicing may result in multiple transcript variants; however, not all variants have been fully described. [provided by RefSeq, Jul 2008]

MS4A3 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_006138.5, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

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=-0.88).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.113 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006138.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MS4A3	NM_006138.5	MANE Select	c.615+44C>T	intron	N/A	NP_006129.4
MS4A3	NM_001031809.2		c.477+44C>T	intron	N/A	NP_001026979.1	Q96HJ5-2
MS4A3	NM_001031666.2		c.246+44C>T	intron	N/A	NP_001026836.1	Q96HJ5-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MS4A3	ENST00000278865.8	TSL:1 MANE Select	c.615+44C>T	intron	N/A	ENSP00000278865.3	Q96HJ5-1
MS4A3	ENST00000358152.6	TSL:5	c.477+44C>T	intron	N/A	ENSP00000350872.2	Q96HJ5-2
MS4A3	ENST00000395032.6	TSL:2	c.246+44C>T	intron	N/A	ENSP00000378473.2	Q96HJ5-3

Frequencies

GnomAD3 genomes

AF:

0.0237

AC:

3603

AN:

152126

Hom.:

124

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0640

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00969

Gnomad ASJ

AF:

0.000865

Gnomad EAS

AF:

0.121

Gnomad SAS

AF:

0.0172

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000911

Gnomad OTH

AF:

0.0148

GnomAD2 exomes

AF:

0.0159

AC:

3984

AN:

249952

AF XY:

0.0142

show subpopulations

Gnomad AFR exome

AF:

0.0651

Gnomad AMR exome

AF:

0.00453

Gnomad ASJ exome

AF:

0.000697

Gnomad EAS exome

AF:

0.119

Gnomad FIN exome

AF:

0.000189

Gnomad NFE exome

AF:

0.00127

Gnomad OTH exome

AF:

0.0103

GnomAD4 exome

AF:

0.00766

AC:

9827

AN:

1283180

Hom.:

445

Cov.:

AF XY:

0.00756

AC XY:

4894

AN XY:

647204

show subpopulations

African (AFR)

AF:

0.0657

AC:

1953

AN:

29738

American (AMR)

AF:

0.00480

AC:

213

AN:

44356

Ashkenazi Jewish (ASJ)

AF:

0.000883

AC:

AN:

24926

East Asian (EAS)

AF:

0.130

AC:

5056

AN:

38746

South Asian (SAS)

AF:

0.0109

AC:

898

AN:

82068

European-Finnish (FIN)

AF:

0.000516

AC:

AN:

52320

Middle Eastern (MID)

AF:

0.00646

AC:

AN:

5422

European-Non Finnish (NFE)

AF:

0.000936

AC:

890

AN:

951100

Other (OTH)

AF:

0.0134

AC:

733

AN:

54504

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

429

858

1286

1715

2144

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

162

324

486

648

810

<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:

0.0237

AC:

3612

AN:

152244

Hom.:

124

Cov.:

AF XY:

0.0242

AC XY:

1800

AN XY:

74456

show subpopulations

African (AFR)

AF:

0.0640

AC:

2658

AN:

41518

American (AMR)

AF:

0.00968

AC:

148

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.000865

AC:

AN:

3468

East Asian (EAS)

AF:

0.121

AC:

626

AN:

5174

South Asian (SAS)

AF:

0.0172

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.0000942

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000911

AC:

AN:

68022

Other (OTH)

AF:

0.0147

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

167

335

502

670

837

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

126

168

210

<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:

0.00945

Hom.:

180

Bravo

AF:

0.0266

Asia WGS

AF:

0.0650

AC:

225

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

1.9

(source)

DANN

Benign

0.47

PhyloP100

-0.14

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over