NM_002443.4:c.216-472G>A

Variant names:

• chr10-46034023-C-T
• rs17178655
• NM_002443.4:c.216-472G>A

Variant summary

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

The NM_002443.4(MSMB):​c.216-472G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.208 in 152,134 control chromosomes in the GnomAD database, including 3,335 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 0.21 (3335 hom., cov: 32)
• Consequence: MSMB NM_002443.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.170
• Publications: 16 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]

ENSG00000305167 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.269 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MSMB	NM_002443.4	c.216-472G>A		intron_variant	Intron 3 of 3	ENST00000582163.3	NP_002434.1
MSMB	NM_138634.3	c.110-472G>A		intron_variant	Intron 2 of 2		NP_619540.1
LOC105378287	XR_945923.4	n.289+1239C>T		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MSMB	ENST00000582163.3	c.216-472G>A		intron_variant	Intron 3 of 3	1	NM_002443.4	ENSP00000463092.1

Frequencies

GnomAD3 genomes AF: 0.208 AC: 31660 AN: 152014 Hom.: 3338 Cov.: 32

Gnomad AFR AF: 0.175

Gnomad AMI AF: 0.167

Gnomad AMR AF: 0.214

Gnomad ASJ AF: 0.210

Gnomad EAS AF: 0.281

Gnomad SAS AF: 0.223

Gnomad FIN AF: 0.194

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.223

Gnomad OTH AF: 0.222

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

GnomAD4 genome AF: 0.208 AC: 31659 AN: 152134 Hom.: 3335 Cov.: 32 AF XY: 0.208 AC XY: 15441 AN XY: 74364

African (AFR) AF: 0.175 AC: 7255 AN: 41496

American (AMR) AF: 0.214 AC: 3269 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.210 AC: 730 AN: 3472

East Asian (EAS) AF: 0.281 AC: 1455 AN: 5170

South Asian (SAS) AF: 0.222 AC: 1071 AN: 4820

European-Finnish (FIN) AF: 0.194 AC: 2053 AN: 10576

Middle Eastern (MID) AF: 0.204 AC: 60 AN: 294

European-Non Finnish (NFE) AF: 0.223 AC: 15152 AN: 68002

Other (OTH) AF: 0.219 AC: 462 AN: 2114

Alfa AF: 0.216 Hom.: 7118

Bravo AF: 0.206

Asia WGS AF: 0.239 AC: 832 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	3.3
DANN	Benign	0.43
PhyloP100		0.17

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

Other links and lift over

dbSNP: rs17178655; hg19: chr10-51561799;