chr7-88301614-G-A

Position:

• chr7-88301614-G-A

Variant summary

Our verdict is Benign. Variant got -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

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]

ENSG00000228113 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
STEAP4	NM_024636.4	c.-3+5178C>T		intron_variant		ENST00000380079.9	NP_078912.2
STEAP4	NM_001205315.2	c.-102+5178C>T		intron_variant			NP_001192244.1
STEAP4	NM_001205316.2	c.-3+5178C>T		intron_variant			NP_001192245.1
LOC124901692	XR_007060420.1	n.824+9304G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STEAP4	ENST00000380079.9	c.-3+5178C>T		intron_variant		1	NM_024636.4	ENSP00000369419.4
STEAP4	ENST00000301959.9	c.-3+5178C>T		intron_variant		1		ENSP00000305545.5
STEAP4	ENST00000414498.1	c.-102+5178C>T		intron_variant		2		ENSP00000394399.1
ENSG00000228113	ENST00000631117.2	n.539-2422G>A		intron_variant		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

Gnomad4 AFR AF: 0.219

Gnomad4 AMR AF: 0.350

Gnomad4 ASJ AF: 0.270

Gnomad4 EAS AF: 0.773

Gnomad4 SAS AF: 0.439

Gnomad4 FIN AF: 0.222

Gnomad4 NFE AF: 0.204

Gnomad4 OTH AF: 0.245

Alfa AF: 0.133 Hom.: 237

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

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: rs12386756; hg19: chr7-87930929;