4-184000146-C-T

Variant names:

• chr4-184000146-C-T
• rs12498735
• NM_020225.3:c.167-1179C>T

Variant summary

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

The NM_020225.3(STOX2):​c.167-1179C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.4 in 151,856 control chromosomes in the GnomAD database, including 13,179 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 0.40 (13179 hom., cov: 31)
• Consequence: STOX2 NM_020225.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.223
• Publications: 6 publications found

Genes affected

STOX2 (HGNC:25450): (storkhead box 2) This gene encodes a Storkhead-box_winged-helix domain containing protein. This protein is differentially expressed in decidual tissue and may be involved in the susceptibility to pre-eclampsia with fetal growth restriction. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Sep 2015]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.565 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STOX2	NM_020225.3	c.167-1179C>T		intron_variant	Intron 1 of 3	ENST00000308497.9	NP_064610.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STOX2	ENST00000308497.9	c.167-1179C>T		intron_variant	Intron 1 of 3	1	NM_020225.3	ENSP00000311257.4
STOX2	ENST00000513034.3	c.365-1179C>T		intron_variant	Intron 1 of 2	3		ENSP00000422118.3
STOX2	ENST00000511250.1	n.414-1179C>T		intron_variant	Intron 1 of 1	4
STOX2	ENST00000512520.1	n.31-1179C>T		intron_variant	Intron 1 of 2	4		ENSP00000425388.2

Frequencies

GnomAD3 genomes AF: 0.400 AC: 60683 AN: 151736 Hom.: 13170 Cov.: 31

Gnomad AFR AF: 0.228

Gnomad AMI AF: 0.520

Gnomad AMR AF: 0.471

Gnomad ASJ AF: 0.323

Gnomad EAS AF: 0.582

Gnomad SAS AF: 0.487

Gnomad FIN AF: 0.550

Gnomad MID AF: 0.418

Gnomad NFE AF: 0.447

Gnomad OTH AF: 0.420

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

GnomAD4 genome AF: 0.400 AC: 60729 AN: 151856 Hom.: 13179 Cov.: 31 AF XY: 0.410 AC XY: 30397 AN XY: 74220

African (AFR) AF: 0.228 AC: 9445 AN: 41410

American (AMR) AF: 0.471 AC: 7196 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.323 AC: 1117 AN: 3458

East Asian (EAS) AF: 0.582 AC: 2988 AN: 5132

South Asian (SAS) AF: 0.489 AC: 2351 AN: 4812

European-Finnish (FIN) AF: 0.550 AC: 5805 AN: 10556

Middle Eastern (MID) AF: 0.408 AC: 120 AN: 294

European-Non Finnish (NFE) AF: 0.447 AC: 30354 AN: 67910

Other (OTH) AF: 0.417 AC: 880 AN: 2108

Alfa AF: 0.421 Hom.: 36590

Bravo AF: 0.387

Asia WGS AF: 0.485 AC: 1689 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.1
DANN	Benign	0.49
PhyloP100		0.22
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: rs12498735; hg19: chr4-184921299;