rs12386756

Variant names:

• chr7-88301614-G-A
• rs12386756
• NM_024636.4:c.-3+5178C>T

Your query was ambiguous. Multiple possible variants found:

• chr7-88301614-G-A
• chr7-88301614-G-C
• chr7-88301614-G-T

Variant summary

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

The NM_024636.4(STEAP4):​c.-3+5178C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.253 in 150,478 control chromosomes in the GnomAD database, including 5,772 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 0.25 (5772 hom., cov: 31)
• Consequence: STEAP4 NM_024636.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.602
• Publications: 4 publications found

Genes affected

STEAP4 (HGNC:21923): (STEAP4 metalloreductase) The protein encoded by this gene belongs to the STEAP (six transmembrane epithelial antigen of prostate) family, and resides in the golgi apparatus. It functions as a metalloreductase that has the ability to reduce both Fe(3+) to Fe(2+) and Cu(2+) to Cu(1+), using NAD(+) as acceptor. Studies in mice and human suggest that this gene maybe involved in adipocyte development and metabolism, and may contribute to the normal biology of the prostate cell, as well as prostate cancer progression. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Apr 2011]

SRI-AS1 (HGNC:40564): (SRI antisense RNA 1)

LOC124901692 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.752 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STEAP4	NM_024636.4	c.-3+5178C>T		intron_variant	Intron 1 of 4	ENST00000380079.9	NP_078912.2
STEAP4	NM_001205315.2	c.-102+5178C>T		intron_variant	Intron 1 of 5		NP_001192244.1
STEAP4	NM_001205316.2	c.-3+5178C>T		intron_variant	Intron 1 of 3		NP_001192245.1
LOC124901692	XR_007060420.1	n.824+9304G>A		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STEAP4	ENST00000380079.9	c.-3+5178C>T		intron_variant	Intron 1 of 4	1	NM_024636.4	ENSP00000369419.4
STEAP4	ENST00000301959.9	c.-3+5178C>T		intron_variant	Intron 1 of 3	1		ENSP00000305545.5
STEAP4	ENST00000414498.1	c.-102+5178C>T		intron_variant	Intron 1 of 3	2		ENSP00000394399.1
SRI-AS1	ENST00000631117.2	n.539-2422G>A		intron_variant	Intron 4 of 4	5

Frequencies

GnomAD3 genomes AF: 0.253 AC: 37999 AN: 150362 Hom.: 5761 Cov.: 31

Gnomad AFR AF: 0.219

Gnomad AMI AF: 0.124

Gnomad AMR AF: 0.350

Gnomad ASJ AF: 0.270

Gnomad EAS AF: 0.772

Gnomad SAS AF: 0.438

Gnomad FIN AF: 0.222

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.205

Gnomad OTH AF: 0.244

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

GnomAD4 genome AF: 0.253 AC: 38028 AN: 150478 Hom.: 5772 Cov.: 31 AF XY: 0.261 AC XY: 19174 AN XY: 73436

African (AFR) AF: 0.219 AC: 8970 AN: 40890

American (AMR) AF: 0.350 AC: 5303 AN: 15148

Ashkenazi Jewish (ASJ) AF: 0.270 AC: 934 AN: 3462

East Asian (EAS) AF: 0.773 AC: 3951 AN: 5114

South Asian (SAS) AF: 0.439 AC: 2088 AN: 4756

European-Finnish (FIN) AF: 0.222 AC: 2284 AN: 10266

Middle Eastern (MID) AF: 0.207 AC: 57 AN: 276

European-Non Finnish (NFE) AF: 0.204 AC: 13819 AN: 67576

Other (OTH) AF: 0.245 AC: 509 AN: 2080

Alfa AF: 0.137 Hom.: 257

Bravo AF: 0.262

Asia WGS AF: 0.571 AC: 1981 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.6
DANN	Benign	0.31
PhyloP100		-0.60
Mutation Taster		=100/0	polymorphism (auto)

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: rs12386756; hg19: chr7-87930929;