chr10-46046508-G-A

Variant names:

• chr10-46046508-G-A
• rs12770171
• ENST00000663171.1:c.-142-129C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000663171.1(MSMB):​c.-142-129C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.154 in 152,278 control chromosomes in the GnomAD database, including 1,998 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 0.15 (1998 hom., cov: 33)
• Consequence: MSMB ENST00000663171.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.368
• Publications: 11 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.209 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000663171.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MSMB	NM_002443.4	MANE Select	c.-271C>T		upstream_gene	N/A	NP_002434.1	P08118-1
	MSMB	NM_138634.3		c.-271C>T		upstream_gene	N/A	NP_619540.1	P08118-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MSMB	ENST00000663171.1		c.-142-129C>T		intron	N/A	ENSP00000499419.1	A0A590UJG9
	MSMB	ENST00000582163.3	TSL:1 MANE Select	c.-271C>T		upstream_gene	N/A	ENSP00000463092.1	P08118-1
	MSMB	ENST00000581478.5	TSL:1	c.-271C>T		upstream_gene	N/A	ENSP00000462641.1	P08118-2

Frequencies

GnomAD3 genomes AF: 0.154 AC: 23489 AN: 152160 Hom.: 2001 Cov.: 33

Gnomad AFR AF: 0.0746

Gnomad AMI AF: 0.103

Gnomad AMR AF: 0.150

Gnomad ASJ AF: 0.233

Gnomad EAS AF: 0.220

Gnomad SAS AF: 0.207

Gnomad FIN AF: 0.136

Gnomad MID AF: 0.323

Gnomad NFE AF: 0.193

Gnomad OTH AF: 0.175

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

GnomAD4 genome AF: 0.154 AC: 23484 AN: 152278 Hom.: 1998 Cov.: 33 AF XY: 0.154 AC XY: 11480 AN XY: 74454

African (AFR) AF: 0.0745 AC: 3097 AN: 41568

American (AMR) AF: 0.150 AC: 2290 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.233 AC: 810 AN: 3472

East Asian (EAS) AF: 0.220 AC: 1138 AN: 5176

South Asian (SAS) AF: 0.207 AC: 999 AN: 4824

European-Finnish (FIN) AF: 0.136 AC: 1444 AN: 10614

Middle Eastern (MID) AF: 0.313 AC: 92 AN: 294

European-Non Finnish (NFE) AF: 0.193 AC: 13155 AN: 68012

Other (OTH) AF: 0.173 AC: 365 AN: 2112

Alfa AF: 0.183 Hom.: 2112

Bravo AF: 0.151

Asia WGS AF: 0.186 AC: 647 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	7.8
DANN	Benign	0.87
PhyloP100		-0.37
PromoterAI		0.013	Neutral

Splicing

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

Other links and lift over

dbSNP: rs12770171; hg19: chr10-51549314;