Genetic Variant ENST00000663171.1:c.-89T>C (chr10-46046326-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000663171.1(MSMB):c.-89T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.581 in 1,161,688 control chromosomes in the GnomAD database, including 200,462 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 0.54 ( 22862 hom., cov: 33)

Exomes 𝑓: 0.59 ( 177600 hom. )

Consequence

MSMB
ENST00000663171.1 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0490

Publications

299 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=-0.87).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.604 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MSMB	NM_002443.4 link	c.-89T>C		upstream_gene_variant		ENST00000582163.3	NP_002434.1	P08118-1
MSMB	NM_138634.3 link	c.-89T>C		upstream_gene_variant			NP_619540.1	P08118-2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
MSMB	ENST00000663171.1 link	c.-89T>C	5_prime_UTR_variant	Exon 2 of 5			ENSP00000499419.1	A0A590UJG9
MSMB	ENST00000582163.3 link	c.-89T>C	upstream_gene_variant		1	NM_002443.4	ENSP00000463092.1	P08118-1
MSMB	ENST00000581478.5 link	c.-89T>C	upstream_gene_variant		1		ENSP00000462641.1	P08118-2

Frequencies

GnomAD3 genomes

AF:

0.538

AC:

81774

AN:

151992

Hom.:

22866

Cov.:

show subpopulations

Gnomad AFR

AF:

0.390

Gnomad AMI

AF:

0.549

Gnomad AMR

AF:

0.593

Gnomad ASJ

AF:

0.516

Gnomad EAS

AF:

0.540

Gnomad SAS

AF:

0.413

Gnomad FIN

AF:

0.646

Gnomad MID

AF:

0.380

Gnomad NFE

AF:

0.609

Gnomad OTH

AF:

0.535

GnomAD4 exome

AF:

0.587

AC:

593099

AN:

1009578

Hom.:

177600

AF XY:

0.580

AC XY:

302844

AN XY:

521818

show subpopulations

African (AFR)

AF:

0.373

AC:

9243

AN:

24804

American (AMR)

AF:

0.659

AC:

28285

AN:

42936

Ashkenazi Jewish (ASJ)

AF:

0.507

AC:

11681

AN:

23058

East Asian (EAS)

AF:

0.546

AC:

20514

AN:

37550

South Asian (SAS)

AF:

0.427

AC:

32354

AN:

75756

European-Finnish (FIN)

AF:

0.650

AC:

34464

AN:

53058

Middle Eastern (MID)

AF:

0.406

AC:

1968

AN:

4850

European-Non Finnish (NFE)

AF:

0.612

AC:

429438

AN:

702170

Other (OTH)

AF:

0.554

AC:

25152

AN:

45396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

12123

24246

36368

48491

60614

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9100

18200

27300

36400

45500

<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:

0.538

AC:

81778

AN:

152110

Hom.:

22862

Cov.:

AF XY:

0.536

AC XY:

39875

AN XY:

74348

show subpopulations

African (AFR)

AF:

0.390

AC:

16158

AN:

41472

American (AMR)

AF:

0.593

AC:

9065

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.516

AC:

1793

AN:

3472

East Asian (EAS)

AF:

0.539

AC:

2787

AN:

5168

South Asian (SAS)

AF:

0.412

AC:

1984

AN:

4818

European-Finnish (FIN)

AF:

0.646

AC:

6845

AN:

10590

Middle Eastern (MID)

AF:

0.391

AC:

115

AN:

294

European-Non Finnish (NFE)

AF:

0.609

AC:

41415

AN:

67992

Other (OTH)

AF:

0.529

AC:

1115

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1877

3753

5630

7506

9383

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

710

1420

2130

2840

3550

<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:

0.581

Hom.:

113411

Bravo

AF:

0.534

Asia WGS

AF:

0.435

AC:

1513

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

2.3

(source)

DANN

Benign

0.60

PhyloP100

-0.049

PromoterAI

0.11

Neutral

(source)

Splicing

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