2-119225674-G-A

Position:

• chr2-119225674-G-A

Variant summary

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

The ENST00000393110.7(STEAP3):​c.-394+1786G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.462 in 152,186 control chromosomes in the GnomAD database, including 16,353 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 0.46 (16353 hom., cov: 34)
• Consequence: STEAP3 ENST00000393110.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.639

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.494 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STEAP3	NM_182915.3	c.-394+1786G>A		intron_variant		ENST00000393110.7	NP_878919.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STEAP3	ENST00000393110.7	c.-394+1786G>A		intron_variant		1	NM_182915.3	ENSP00000376822
STEAP3	ENST00000393106.6	c.-77+1786G>A		intron_variant		1		ENSP00000376818	P1
STEAP3	ENST00000393107.2	c.-9+1786G>A		intron_variant		1		ENSP00000376819	P1
STEAP3	ENST00000409811.5	c.-9+1786G>A		intron_variant		1		ENSP00000386510

Frequencies

GnomAD3 genomes AF: 0.462 AC: 70194 AN: 152068 Hom.: 16338 Cov.: 34

Gnomad AFR AF: 0.459

Gnomad AMI AF: 0.393

Gnomad AMR AF: 0.407

Gnomad ASJ AF: 0.485

Gnomad EAS AF: 0.356

Gnomad SAS AF: 0.344

Gnomad FIN AF: 0.413

Gnomad MID AF: 0.472

Gnomad NFE AF: 0.498

Gnomad OTH AF: 0.488

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

GnomAD4 genome AF: 0.462 AC: 70243 AN: 152186 Hom.: 16353 Cov.: 34 AF XY: 0.453 AC XY: 33733 AN XY: 74402

Gnomad4 AFR AF: 0.459

Gnomad4 AMR AF: 0.407

Gnomad4 ASJ AF: 0.485

Gnomad4 EAS AF: 0.357

Gnomad4 SAS AF: 0.345

Gnomad4 FIN AF: 0.413

Gnomad4 NFE AF: 0.498

Gnomad4 OTH AF: 0.489

Alfa AF: 0.471 Hom.: 4001

Bravo AF: 0.462

Asia WGS AF: 0.326 AC: 1134 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	6.8
DANN	Benign	0.82

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: rs865688; hg19: chr2-119983250; COSMIC: COSV61528261;