rs2070770

Variant names:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_152866.3(MS4A1):c.216C>T(p.Ile72Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0784 in 1,614,060 control chromosomes in the GnomAD database, including 5,805 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.056 ( 323 hom., cov: 32)

Exomes 𝑓: 0.081 ( 5482 hom. )

Consequence

MS4A1
NM_152866.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.427

Publications

16 publications found

Variant links:

Genes affected

MS4A1 (HGNC:7315): (membrane spanning 4-domains A1) 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. This gene encodes a B-lymphocyte surface molecule which plays a role in the development and differentiation of B-cells into plasma cells. This family member is localized to 11q12, among a cluster of family members. Alternative splicing of this gene results in two transcript variants which encode the same protein. [provided by RefSeq, Jul 2008]

MS4A1 Gene-Disease associations (from GenCC):

common variable immunodeficiency
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
immunodeficiency, common variable, 5
Inheritance: AR, Unknown Classification: LIMITED Submitted by: ClinGen, Labcorp Genetics (formerly Invitae)

MS4A1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.42).

BP6

Variant 11-60463058-C-T is Benign according to our data. Variant chr11-60463058-C-T is described in ClinVar as Benign. ClinVar VariationId is 618716.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.427 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.157 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MS4A1	NM_152866.3 link	c.216C>T	p.Ile72Ile	synonymous_variant	Exon 4 of 8	ENST00000345732.9	NP_690605.1	P11836-1A0A024R507
MS4A1	NM_021950.4 link	c.216C>T	p.Ile72Ile	synonymous_variant	Exon 3 of 7		NP_068769.2	P11836-1A0A024R507
MS4A1	NM_152867.2 link	c.216C>T	p.Ile72Ile	synonymous_variant	Exon 3 of 7		NP_690606.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MS4A1	ENST00000345732.9 link	c.216C>T	p.Ile72Ile	synonymous_variant	Exon 4 of 8	1	NM_152866.3	ENSP00000314620.7		P11836-1

Frequencies

GnomAD3 genomes

AF:

0.0565

AC:

8598

AN:

152116

Hom.:

323

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0199

Gnomad AMI

AF:

0.110

Gnomad AMR

AF:

0.0386

Gnomad ASJ

AF:

0.0441

Gnomad EAS

AF:

0.101

Gnomad SAS

AF:

0.166

Gnomad FIN

AF:

0.0315

Gnomad MID

AF:

0.0380

Gnomad NFE

AF:

0.0758

Gnomad OTH

AF:

0.0499

GnomAD2 exomes

AF:

0.0714

AC:

17942

AN:

251282

AF XY:

0.0780

show subpopulations

Gnomad AFR exome

AF:

0.0189

Gnomad AMR exome

AF:

0.0277

Gnomad ASJ exome

AF:

0.0402

Gnomad EAS exome

AF:

0.0950

Gnomad FIN exome

AF:

0.0345

Gnomad NFE exome

AF:

0.0757

Gnomad OTH exome

AF:

0.0549

GnomAD4 exome

AF:

0.0807

AC:

117930

AN:

1461826

Hom.:

5482

Cov.:

AF XY:

0.0834

AC XY:

60622

AN XY:

727206

show subpopulations

African (AFR)

AF:

0.0184

AC:

617

AN:

33480

American (AMR)

AF:

0.0287

AC:

1284

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0412

AC:

1076

AN:

26134

East Asian (EAS)

AF:

0.127

AC:

5044

AN:

39698

South Asian (SAS)

AF:

0.158

AC:

13665

AN:

86256

European-Finnish (FIN)

AF:

0.0365

AC:

1951

AN:

53406

Middle Eastern (MID)

AF:

0.0579

AC:

334

AN:

5766

European-Non Finnish (NFE)

AF:

0.0807

AC:

89757

AN:

1111970

Other (OTH)

AF:

0.0696

AC:

4202

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

6257

12515

18772

25030

31287

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3462

6924

10386

13848

17310

<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:

0.0565

AC:

8596

AN:

152234

Hom.:

323

Cov.:

AF XY:

0.0566

AC XY:

4212

AN XY:

74456

show subpopulations

African (AFR)

AF:

0.0199

AC:

828

AN:

41540

American (AMR)

AF:

0.0385

AC:

588

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.0441

AC:

153

AN:

3472

East Asian (EAS)

AF:

0.101

AC:

521

AN:

5184

South Asian (SAS)

AF:

0.166

AC:

801

AN:

4822

European-Finnish (FIN)

AF:

0.0315

AC:

334

AN:

10616

Middle Eastern (MID)

AF:

0.0408

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0758

AC:

5155

AN:

68002

Other (OTH)

AF:

0.0493

AC:

104

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

416

833

1249

1666

2082

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

110

220

330

440

550

<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:

0.0722

Hom.:

413

Bravo

AF:

0.0524

Asia WGS

AF:

0.130

AC:

453

AN:

3478

EpiCase

AF:

0.0766

EpiControl

AF:

0.0775

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jun 09, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Immunodeficiency, common variable, 5

Benign:1

Nov 01, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.42

CADD

Benign

8.0

(source)

DANN

Benign

0.69

PhyloP100

-0.43

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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over