7-88298077-G-C

Variant names:

• chr7-88298077-G-C
• rs10263111
• NM_024636.4:c.-3+8715C>G

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+8715C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.475 in 151,778 control chromosomes in the GnomAD database, including 17,710 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 0.47 (17710 hom., cov: 31)
• Consequence: STEAP4 NM_024636.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.31
• 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=-1.09).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.814 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024636.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STEAP4	NM_024636.4	MANE Select	c.-3+8715C>G		intron	N/A	NP_078912.2
	STEAP4	NM_001205315.2		c.-101-7063C>G		intron	N/A	NP_001192244.1
	STEAP4	NM_001205316.2		c.-3+8715C>G		intron	N/A	NP_001192245.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STEAP4	ENST00000380079.9	TSL:1 MANE Select	c.-3+8715C>G		intron	N/A	ENSP00000369419.4
	STEAP4	ENST00000301959.9	TSL:1	c.-3+8715C>G		intron	N/A	ENSP00000305545.5
	STEAP4	ENST00000879105.1		c.-101-7063C>G		intron	N/A	ENSP00000549164.1

Frequencies

GnomAD3 genomes AF: 0.475 AC: 72010 AN: 151660 Hom.: 17697 Cov.: 31

Gnomad AFR AF: 0.422

Gnomad AMI AF: 0.506

Gnomad AMR AF: 0.572

Gnomad ASJ AF: 0.534

Gnomad EAS AF: 0.835

Gnomad SAS AF: 0.629

Gnomad FIN AF: 0.380

Gnomad MID AF: 0.424

Gnomad NFE AF: 0.457

Gnomad OTH AF: 0.509

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

GnomAD4 genome AF: 0.475 AC: 72063 AN: 151778 Hom.: 17710 Cov.: 31 AF XY: 0.478 AC XY: 35406 AN XY: 74118

African (AFR) AF: 0.423 AC: 17497 AN: 41392

American (AMR) AF: 0.571 AC: 8703 AN: 15234

Ashkenazi Jewish (ASJ) AF: 0.534 AC: 1853 AN: 3470

East Asian (EAS) AF: 0.835 AC: 4317 AN: 5172

South Asian (SAS) AF: 0.630 AC: 3028 AN: 4808

European-Finnish (FIN) AF: 0.380 AC: 3987 AN: 10492

Middle Eastern (MID) AF: 0.435 AC: 128 AN: 294

European-Non Finnish (NFE) AF: 0.457 AC: 31025 AN: 67906

Other (OTH) AF: 0.507 AC: 1066 AN: 2102

Alfa AF: 0.461 Hom.: 1993

Bravo AF: 0.487

Asia WGS AF: 0.693 AC: 2408 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.27
DANN	Benign	0.32
PhyloP100		-2.3
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: rs10263111; hg19: chr7-87927392;