rs1867749

chr2-119256336-C-Gchr2-119256336-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_182915.3(STEAP3):c.1215+1488C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.362 in 151,998 control chromosomes in the GnomAD database, including 10,574 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 0.36 (10574 hom., cov: 32)
• Consequence: STEAP3 NM_182915.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0710

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.437 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STEAP3	NM_182915.3	c.1215+1488C>G		intron_variant		ENST00000393110.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STEAP3	ENST00000393110.7	c.1215+1488C>G		intron_variant		1	NM_182915.3
STEAP3-AS1	ENST00000654197.1	n.112-7974G>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.362 AC: 54971 AN: 151882 Hom.: 10567 Cov.: 32

Gnomad AFR AF: 0.240

Gnomad AMI AF: 0.250

Gnomad AMR AF: 0.330

Gnomad ASJ AF: 0.370

Gnomad EAS AF: 0.329

Gnomad SAS AF: 0.309

Gnomad FIN AF: 0.421

Gnomad MID AF: 0.329

Gnomad NFE AF: 0.441

Gnomad OTH AF: 0.390

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

GnomAD4 genome AF: 0.362 AC: 54996 AN: 151998 Hom.: 10574 Cov.: 32 AF XY: 0.360 AC XY: 26733 AN XY: 74300

Gnomad4 AFR AF: 0.240

Gnomad4 AMR AF: 0.330

Gnomad4 ASJ AF: 0.370

Gnomad4 EAS AF: 0.328

Gnomad4 SAS AF: 0.311

Gnomad4 FIN AF: 0.421

Gnomad4 NFE AF: 0.441

Gnomad4 OTH AF: 0.391

Alfa AF: 0.254 Hom.: 622

Bravo AF: 0.347

Asia WGS AF: 0.294 AC: 1023 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	0.61
Dann	Benign	0.42

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: rs1867749; hg19: chr2-120013912; COSMIC: COSV61528344;