4-184000146-C-T

Position:

• chr4-184000146-C-T

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	UniProt
STOX2	NM_020225.3	c.167-1179C>T		intron_variant		ENST00000308497.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STOX2	ENST00000308497.9	c.167-1179C>T		intron_variant		1	NM_020225.3	P1
STOX2	ENST00000513034.3	c.365-1179C>T		intron_variant		3
STOX2	ENST00000512520.1	c.33-1179C>T		intron_variant, NMD_transcript_variant		4
STOX2	ENST00000511250.1	n.414-1179C>T		intron_variant, non_coding_transcript_variant		4

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

Gnomad4 AFR AF: 0.228

Gnomad4 AMR AF: 0.471

Gnomad4 ASJ AF: 0.323

Gnomad4 EAS AF: 0.582

Gnomad4 SAS AF: 0.489

Gnomad4 FIN AF: 0.550

Gnomad4 NFE AF: 0.447

Gnomad4 OTH AF: 0.417

Alfa AF: 0.427 Hom.: 14050

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

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: rs12498735; hg19: chr4-184921299;