dbSNP rs10994470: MSMB:c.215+1804G>A (chr10-46037162-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_002443.4(MSMB):c.215+1804G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0254 in 152,306 control chromosomes in the GnomAD database, including 79 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 0.025 ( 79 hom., cov: 33)

Consequence

MSMB
NM_002443.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.447

Publications

4 publications found

Variant links:

Genes affected

MSMB (HGNC:7372): (microseminoprotein beta) The protein encoded by this gene is a member of the immunoglobulin binding factor family. It is synthesized by the epithelial cells of the prostate gland and secreted into the seminal plasma. This protein has inhibin-like activity. It may have a role as an autocrine paracrine factor in uterine, breast and other female reproductive tissues. The expression of the encoded protein is found to be decreased in prostate cancer. Two alternatively spliced transcript variants encoding different isoforms are described for this gene. The use of alternate polyadenylation sites has been found for this gene. [provided by RefSeq, Jul 2008]

MSMB 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=-0.85).

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0254 (3871/152306) while in subpopulation NFE AF = 0.0392 (2666/68030). AF 95% confidence interval is 0.0379. There are 79 homozygotes in GnomAd4. There are 1799 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 79 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MSMB	NM_002443.4 link	c.215+1804G>A		intron_variant	Intron 3 of 3	ENST00000582163.3	NP_002434.1	P08118-1
MSMB	NM_138634.3 link	c.109+2824G>A		intron_variant	Intron 2 of 2		NP_619540.1	P08118-2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
MSMB	ENST00000582163.3 link	c.215+1804G>A	intron_variant	Intron 3 of 3	1	NM_002443.4	ENSP00000463092.1	P08118-1
MSMB	ENST00000581478.5 link	c.109+2824G>A	intron_variant	Intron 2 of 2	1		ENSP00000462641.1	P08118-2
MSMB	ENST00000663171.1 link	c.215+1804G>A	intron_variant	Intron 4 of 4			ENSP00000499419.1	A0A590UJG9

Frequencies

GnomAD3 genomes

AF:

0.0254

AC:

3872

AN:

152188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00690

Gnomad AMI

AF:

0.0461

Gnomad AMR

AF:

0.0201

Gnomad ASJ

AF:

0.0366

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.0122

Gnomad FIN

AF:

0.0303

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.0392

Gnomad OTH

AF:

0.0282

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.0254

AC:

3871

AN:

152306

Hom.:

Cov.:

AF XY:

0.0242

AC XY:

1799

AN XY:

74456

show subpopulations

African (AFR)

AF:

0.00688

AC:

286

AN:

41580

American (AMR)

AF:

0.0201

AC:

307

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.0366

AC:

127

AN:

3468

East Asian (EAS)

AF:

0.000386

AC:

AN:

5180

South Asian (SAS)

AF:

0.0120

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.0303

AC:

321

AN:

10600

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0392

AC:

2666

AN:

68030

Other (OTH)

AF:

0.0279

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

207

414

620

827

1034

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

132

176

220

<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:

0.0343

Hom.:

130

Bravo

AF:

0.0241

Asia WGS

AF:

0.00375

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.89

(source)

DANN

Benign

0.67

PhyloP100

-0.45

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over