10-46037162-C-T

Position:

• chr10-46037162-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.447

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]

ACMG classification

Verdict is Benign. Variant got -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 male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 79 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MSMB	NM_002443.4	c.215+1804G>A		intron_variant		ENST00000582163.3	NP_002434.1
MSMB	NM_138634.3	c.109+2824G>A		intron_variant			NP_619540.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MSMB	ENST00000582163.3	c.215+1804G>A		intron_variant		1	NM_002443.4	ENSP00000463092.1
MSMB	ENST00000581478.5	c.109+2824G>A		intron_variant		1		ENSP00000462641.1
MSMB	ENST00000663171.1	c.215+1804G>A		intron_variant				ENSP00000499419.1

Frequencies

GnomAD3 genomes AF: 0.0254 AC: 3872 AN: 152188 Hom.: 80 Cov.: 33

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.: 79 Cov.: 33 AF XY: 0.0242 AC XY: 1799 AN XY: 74456

Gnomad4 AFR AF: 0.00688

Gnomad4 AMR AF: 0.0201

Gnomad4 ASJ AF: 0.0366

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.0120

Gnomad4 FIN AF: 0.0303

Gnomad4 NFE AF: 0.0392

Gnomad4 OTH AF: 0.0279

Alfa AF: 0.0350 Hom.: 88

Bravo AF: 0.0241

Asia WGS AF: 0.00375 AC: 13 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
DANN	Benign	0.67

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

LitVar

Other links and lift over

dbSNP: rs10994470; hg19: chr10-51558660;