Genetic Variant MSRB2:c.219+95A>T (chr10-23104339-A-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_012228.4(MSRB2):c.219+95A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.226 in 912,040 control chromosomes in the GnomAD database, including 24,550 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 0.19 ( 3156 hom., cov: 31)

Exomes 𝑓: 0.23 ( 21394 hom. )

Consequence

MSRB2
NM_012228.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.319

Publications

0 publications found

Variant links:

Genes affected

MSRB2 (HGNC:17061): (methionine sulfoxide reductase B2) Predicted to enable actin binding activity; peptide-methionine (R)-S-oxide reductase activity; and zinc ion binding activity. Predicted to be involved in actin filament polymerization and protein repair. Predicted to be located in mitochondrion. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

MSRB2 links:

ENSG00000286924 (HGNC:):

ENSG00000286924 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=-0.91).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.264 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MSRB2	NM_012228.4 link	c.219+95A>T		intron_variant	Intron 2 of 4	ENST00000376510.8	NP_036360.3	Q9Y3D2
MSRB2	XM_011519426.3 link	c.219+95A>T		intron_variant	Intron 2 of 3		XP_011517728.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
MSRB2	ENST00000376510.8 link	c.219+95A>T	intron_variant	Intron 2 of 4	1	NM_012228.4	ENSP00000365693.3	Q9Y3D2
MSRB2	ENST00000472663.1 link	n.99+95A>T	intron_variant	Intron 1 of 4	5		ENSP00000434990.1	H0YE51
ENSG00000286924	ENST00000655462.1 link	n.116+29350T>A	intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes

AF:

0.185

AC:

28153

AN:

151776

Hom.:

3157

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0535

Gnomad AMI

AF:

0.256

Gnomad AMR

AF:

0.183

Gnomad ASJ

AF:

0.198

Gnomad EAS

AF:

0.276

Gnomad SAS

AF:

0.269

Gnomad FIN

AF:

0.301

Gnomad MID

AF:

0.152

Gnomad NFE

AF:

0.234

Gnomad OTH

AF:

0.204

GnomAD4 exome

AF:

0.234

AC:

178106

AN:

760146

Hom.:

21394

AF XY:

0.236

AC XY:

92334

AN XY:

391758

show subpopulations

African (AFR)

AF:

0.0474

AC:

840

AN:

17706

American (AMR)

AF:

0.167

AC:

4163

AN:

24914

Ashkenazi Jewish (ASJ)

AF:

0.192

AC:

3192

AN:

16620

East Asian (EAS)

AF:

0.251

AC:

7623

AN:

30380

South Asian (SAS)

AF:

0.256

AC:

14054

AN:

54884

European-Finnish (FIN)

AF:

0.294

AC:

13797

AN:

46946

Middle Eastern (MID)

AF:

0.169

AC:

445

AN:

2638

European-Non Finnish (NFE)

AF:

0.237

AC:

125825

AN:

530070

Other (OTH)

AF:

0.227

AC:

8167

AN:

35988

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

6480

12960

19441

25921

32401

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3150

6300

9450

12600

15750

<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:

0.185

AC:

28159

AN:

151894

Hom.:

3156

Cov.:

AF XY:

0.190

AC XY:

14073

AN XY:

74216

show subpopulations

African (AFR)

AF:

0.0536

AC:

2221

AN:

41460

American (AMR)

AF:

0.183

AC:

2795

AN:

15260

Ashkenazi Jewish (ASJ)

AF:

0.198

AC:

687

AN:

3470

East Asian (EAS)

AF:

0.275

AC:

1417

AN:

5144

South Asian (SAS)

AF:

0.269

AC:

1284

AN:

4774

European-Finnish (FIN)

AF:

0.301

AC:

3171

AN:

10540

Middle Eastern (MID)

AF:

0.139

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.234

AC:

15876

AN:

67932

Other (OTH)

AF:

0.206

AC:

434

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1104

2208

3312

4416

5520

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

316

632

948

1264

1580

<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:

0.214

Hom.:

495

Bravo

AF:

0.168

Asia WGS

AF:

0.293

AC:

1016

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

4.0

(source)

DANN

Benign

0.63

PhyloP100

-0.32

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