rs4592854

Variant names:

• chr2-119248291-G-A
• rs4592854
• NM_182915.3:c.1050+85G>A

Your query was ambiguous. Multiple possible variants found:

• chr2-119248291-G-A
• chr2-119248291-G-C
• chr2-119248291-G-T

Variant summary

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

The NM_182915.3(STEAP3):​c.1050+85G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0563 in 1,453,342 control chromosomes in the GnomAD database, including 2,500 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 0.066 (403 hom., cov: 32)
  • Exomes 𝑓: 0.055 (2097 hom.)
• Consequence: STEAP3 NM_182915.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.37
• Publications: 2 publications found

Genes affected

STEAP3 (HGNC:24592): (STEAP3 metalloreductase) This gene encodes a multipass membrane protein that functions as an iron transporter. The encoded protein can reduce both iron (Fe3+) and copper (Cu2+) cations. This protein may mediate downstream responses to p53, including promoting apoptosis. Deficiency in this gene can cause anemia. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2015]

STEAP3-AS1 (HGNC:41053): (STEAP3 antisense RNA 1)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0966 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_182915.3. 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
	STEAP3	NM_182915.3	MANE Select	c.1050+85G>A		intron	N/A	NP_878919.2
	STEAP3	NM_001008410.2		c.1020+85G>A		intron	N/A	NP_001008410.1
	STEAP3	NM_018234.3		c.1020+85G>A		intron	N/A	NP_060704.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STEAP3	ENST00000393110.7	TSL:1 MANE Select	c.1050+85G>A		intron	N/A	ENSP00000376822.2
	STEAP3	ENST00000393106.6	TSL:1	c.1020+85G>A		intron	N/A	ENSP00000376818.2
	STEAP3	ENST00000393107.2	TSL:1	c.1020+85G>A		intron	N/A	ENSP00000376819.2

Frequencies

GnomAD3 genomes AF: 0.0663 AC: 10047 AN: 151594 Hom.: 391 Cov.: 32

Gnomad AFR AF: 0.0985

Gnomad AMI AF: 0.0702

Gnomad AMR AF: 0.0450

Gnomad ASJ AF: 0.0678

Gnomad EAS AF: 0.0110

Gnomad SAS AF: 0.0861

Gnomad FIN AF: 0.0508

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0566

Gnomad OTH AF: 0.0707

GnomAD4 exome AF: 0.0551 AC: 71683 AN: 1301630 Hom.: 2097 Cov.: 22 AF XY: 0.0554 AC XY: 35336 AN XY: 637566

African (AFR) AF: 0.0961 AC: 2846 AN: 29626

American (AMR) AF: 0.0346 AC: 1086 AN: 31386

Ashkenazi Jewish (ASJ) AF: 0.0598 AC: 1191 AN: 19906

East Asian (EAS) AF: 0.00771 AC: 291 AN: 37758

South Asian (SAS) AF: 0.0775 AC: 5362 AN: 69202

European-Finnish (FIN) AF: 0.0527 AC: 1804 AN: 34244

Middle Eastern (MID) AF: 0.0468 AC: 244 AN: 5216

European-Non Finnish (NFE) AF: 0.0549 AC: 55964 AN: 1019878

Other (OTH) AF: 0.0532 AC: 2895 AN: 54414

GnomAD4 genome AF: 0.0665 AC: 10086 AN: 151712 Hom.: 403 Cov.: 32 AF XY: 0.0647 AC XY: 4794 AN XY: 74120

African (AFR) AF: 0.0992 AC: 4091 AN: 41256

American (AMR) AF: 0.0449 AC: 686 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.0678 AC: 235 AN: 3464

East Asian (EAS) AF: 0.0110 AC: 57 AN: 5172

South Asian (SAS) AF: 0.0862 AC: 414 AN: 4802

European-Finnish (FIN) AF: 0.0508 AC: 532 AN: 10472

Middle Eastern (MID) AF: 0.0544 AC: 16 AN: 294

European-Non Finnish (NFE) AF: 0.0566 AC: 3844 AN: 67960

Other (OTH) AF: 0.0699 AC: 147 AN: 2102

Alfa AF: 0.0624 Hom.: 89

Bravo AF: 0.0659

Asia WGS AF: 0.0570 AC: 199 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.15
DANN	Benign	0.62
PhyloP100		-2.4
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: rs4592854; hg19: chr2-120005867;