10-46037697-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002443.4(MSMB):c.215+1269T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.466 in 152,044 control chromosomes in the GnomAD database, including 18,444 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 0.47 (18444 hom., cov: 32)
• Consequence: MSMB NM_002443.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.301

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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.711 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MSMB	NM_002443.4	c.215+1269T>C		intron_variant		ENST00000582163.3
MSMB	NM_138634.3	c.109+2289T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MSMB	ENST00000582163.3	c.215+1269T>C		intron_variant		1	NM_002443.4	P1
MSMB	ENST00000581478.5	c.109+2289T>C		intron_variant		1
MSMB	ENST00000663171.1	c.215+1269T>C		intron_variant

Frequencies

GnomAD3 genomes AF: 0.466 AC: 70861 AN: 151924 Hom.: 18416 Cov.: 32

Gnomad AFR AF: 0.718

Gnomad AMI AF: 0.339

Gnomad AMR AF: 0.390

Gnomad ASJ AF: 0.415

Gnomad EAS AF: 0.362

Gnomad SAS AF: 0.347

Gnomad FIN AF: 0.333

Gnomad MID AF: 0.426

Gnomad NFE AF: 0.372

Gnomad OTH AF: 0.461

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

GnomAD4 genome AF: 0.466 AC: 70926 AN: 152044 Hom.: 18444 Cov.: 32 AF XY: 0.461 AC XY: 34254 AN XY: 74338

Gnomad4 AFR AF: 0.718

Gnomad4 AMR AF: 0.389

Gnomad4 ASJ AF: 0.415

Gnomad4 EAS AF: 0.362

Gnomad4 SAS AF: 0.346

Gnomad4 FIN AF: 0.333

Gnomad4 NFE AF: 0.372

Gnomad4 OTH AF: 0.454

Alfa AF: 0.367 Hom.: 6349

Bravo AF: 0.481

Asia WGS AF: 0.381 AC: 1325 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	0.68
Dann	Benign	0.57

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: rs7076948; hg19: chr10-51558125;