chr2-119225674-G-A

Variant names:

• chr2-119225674-G-A
• rs865688
• NM_182915.3:c.-394+1786G>A

Variant summary

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

The NM_182915.3(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 NM_182915.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.639
• Publications: 6 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 Gene-Disease associations (from GenCC):

• severe congenital hypochromic anemia with ringed sideroblasts

  Inheritance: AD, Unknown Classification: MODERATE, SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Genomics England PanelApp, Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
STEAP3	NM_182915.3	c.-394+1786G>A		intron_variant	Intron 1 of 5	ENST00000393110.7	NP_878919.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STEAP3	ENST00000393110.7	c.-394+1786G>A		intron_variant	Intron 1 of 5	1	NM_182915.3	ENSP00000376822.2
STEAP3	ENST00000393106.6	c.-77+1786G>A		intron_variant	Intron 1 of 5	1		ENSP00000376818.2
STEAP3	ENST00000393107.2	c.-9+1786G>A		intron_variant	Intron 1 of 4	1		ENSP00000376819.2
STEAP3	ENST00000409811.5	c.-9+1786G>A		intron_variant	Intron 1 of 5	1		ENSP00000386510.1

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

African (AFR) AF: 0.459 AC: 19062 AN: 41536

American (AMR) AF: 0.407 AC: 6220 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.485 AC: 1685 AN: 3472

East Asian (EAS) AF: 0.357 AC: 1844 AN: 5172

South Asian (SAS) AF: 0.345 AC: 1666 AN: 4824

European-Finnish (FIN) AF: 0.413 AC: 4373 AN: 10592

Middle Eastern (MID) AF: 0.473 AC: 139 AN: 294

European-Non Finnish (NFE) AF: 0.498 AC: 33864 AN: 67980

Other (OTH) AF: 0.489 AC: 1032 AN: 2112

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
PhyloP100		0.64
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: rs865688; hg19: chr2-119983250; COSMIC: COSV61528261;