dbSNP rs17155019: MS4A1:c.-171C>T (chr11-60462204-C-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_152866.3(MS4A1):c.-171C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00846 in 753,748 control chromosomes in the GnomAD database, including 269 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.011 ( 77 hom., cov: 32)

Exomes 𝑓: 0.0078 ( 192 hom. )

Consequence

MS4A1
NM_152866.3 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.130

Publications

3 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 11-60462204-C-T is Benign according to our data. Variant chr11-60462204-C-T is described in ClinVar as Benign. ClinVar VariationId is 1229170.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0827 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
MS4A1	NM_152866.3 link	c.-171C>T	5_prime_UTR_variant	Exon 3 of 8	ENST00000345732.9	NP_690605.1
MS4A1	NM_152867.2 link	c.-171C>T	5_prime_UTR_variant	Exon 2 of 7		NP_690606.1
MS4A1	NM_021950.4 link	c.-16-155C>T	intron_variant	Intron 1 of 6		NP_068769.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MS4A1	ENST00000345732.9 link	c.-171C>T		5_prime_UTR_variant	Exon 3 of 8	1	NM_152866.3	ENSP00000314620.7

Frequencies

GnomAD3 genomes

AF:

0.0109

AC:

1654

AN:

152130

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00174

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0864

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0354

Gnomad SAS

AF:

0.00228

Gnomad FIN

AF:

0.000189

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000676

Gnomad OTH

AF:

0.0100

GnomAD2 exomes

AF:

0.0202

AC:

2862

AN:

141792

AF XY:

0.0164

show subpopulations

Gnomad AFR exome

AF:

0.000571

Gnomad AMR exome

AF:

0.0904

Gnomad ASJ exome

AF:

0.000119

Gnomad EAS exome

AF:

0.0430

Gnomad FIN exome

AF:

0.000319

Gnomad NFE exome

AF:

0.000471

Gnomad OTH exome

AF:

0.0154

GnomAD4 exome

AF:

0.00785

AC:

4721

AN:

601500

Hom.:

192

Cov.:

AF XY:

0.00669

AC XY:

2156

AN XY:

322240

show subpopulations

African (AFR)

AF:

0.00114

AC:

AN:

16628

American (AMR)

AF:

0.0929

AC:

3184

AN:

34286

Ashkenazi Jewish (ASJ)

AF:

0.0000501

AC:

AN:

19942

East Asian (EAS)

AF:

0.0270

AC:

842

AN:

31128

South Asian (SAS)

AF:

0.00221

AC:

140

AN:

63288

European-Finnish (FIN)

AF:

0.000150

AC:

AN:

33266

Middle Eastern (MID)

AF:

0.000241

AC:

AN:

4142

European-Non Finnish (NFE)

AF:

0.000645

AC:

237

AN:

367310

Other (OTH)

AF:

0.00927

AC:

292

AN:

31510

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

274

548

822

1096

1370

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

144

192

240

<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:

0.0109

AC:

1659

AN:

152248

Hom.:

Cov.:

AF XY:

0.0129

AC XY:

964

AN XY:

74440

show subpopulations

African (AFR)

AF:

0.00173

AC:

AN:

41550

American (AMR)

AF:

0.0866

AC:

1324

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.0356

AC:

184

AN:

5164

South Asian (SAS)

AF:

0.00207

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.000189

AC:

AN:

10608

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000676

AC:

AN:

68024

Other (OTH)

AF:

0.00994

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

155

233

310

388

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00729

Hom.:

Bravo

AF:

0.0161

Asia WGS

AF:

0.0150

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jun 20, 2021

GeneDx

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

-0.83

CADD

Benign

5.9

(source)

DANN

Benign

0.51

PhyloP100

-0.13

PromoterAI

-0.050

Neutral

(source)

Mutation Taster

=300/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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