rs41274660

Positions:

• chr10-46046289-A-C

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The ENST00000663171.1(MSMB):​c.-52T>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0108 in 1,579,506 control chromosomes in the GnomAD database, including 99 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 0.0076 (6 hom., cov: 34)
  • Exomes 𝑓: 0.011 (93 hom.)
• Consequence: MSMB ENST00000663171.1 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.588

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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BS2: High Homozygotes in GnomAd4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MSMB	NM_002443.4			upstream_gene_variant		ENST00000582163.3
MSMB	NM_138634.3			upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MSMB	ENST00000663171.1	c.-52T>G		5_prime_UTR_variant	2/5
MSMB	ENST00000582163.3			upstream_gene_variant		1	NM_002443.4	P1
MSMB	ENST00000581478.5			upstream_gene_variant		1

Frequencies

GnomAD3 genomes AF: 0.00759 AC: 1155 AN: 152232 Hom.: 6 Cov.: 34

Gnomad AFR AF: 0.00265

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.00550

Gnomad ASJ AF: 0.0216

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00104

Gnomad FIN AF: 0.00358

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0121

Gnomad OTH AF: 0.00766

GnomAD4 exome AF: 0.0111 AC: 15859 AN: 1427156 Hom.: 93 Cov.: 26 AF XY: 0.0108 AC XY: 7696 AN XY: 712332

Gnomad4 AFR exome AF: 0.00158

Gnomad4 AMR exome AF: 0.00645

Gnomad4 ASJ exome AF: 0.0189

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00171

Gnomad4 FIN exome AF: 0.00611

Gnomad4 NFE exome AF: 0.0129

Gnomad4 OTH exome AF: 0.0102

GnomAD4 genome AF: 0.00758 AC: 1155 AN: 152350 Hom.: 6 Cov.: 34 AF XY: 0.00701 AC XY: 522 AN XY: 74502

Gnomad4 AFR AF: 0.00264

Gnomad4 AMR AF: 0.00549

Gnomad4 ASJ AF: 0.0216

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00104

Gnomad4 FIN AF: 0.00358

Gnomad4 NFE AF: 0.0121

Gnomad4 OTH AF: 0.00758

Alfa AF: 0.0108 Hom.: 4

Bravo AF: 0.00829

Asia WGS AF: 0.00144 AC: 5 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	0.40
DANN	Benign	0.81

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs41274660; hg19: chr10-51549533;