rs1544295

Positions:

• chr13-42924553-C-T

Variant summary

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

The NM_033255.5(EPSTI1):​c.657+1783G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.166 in 152,152 control chromosomes in the GnomAD database, including 2,139 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 0.17 (2139 hom., cov: 32)
• Consequence: EPSTI1 NM_033255.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.07

Genes affected

EPSTI1 (HGNC:16465): (epithelial stromal interaction 1) The protein encoded by this gene has been shown to promote tumor invasion and metastasis in some invasive cancer cells when overexpressed. Expression of this gene has been shown to be upregulated by direct binding of the Kruppel like factor 8 protein to promoter sequences. The translated protein interacts with the amino terminal region of the valosin containing protein gene product, resulting in the nuclear translocation of the nuclear factor kappa B subunit 1 gene product, and activation of target genes. Overexpression of this gene has been observed in some breast cancers and in some individuals with systemic lupus erythematosus (SLE). [provided by RefSeq, Sep 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.178 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EPSTI1	NM_033255.5	c.657+1783G>A		intron_variant		ENST00000313624.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EPSTI1	ENST00000313624.12	c.657+1783G>A		intron_variant		1	NM_033255.5	P4

Frequencies

GnomAD3 genomes AF: 0.166 AC: 25262 AN: 152034 Hom.: 2132 Cov.: 32

Gnomad AFR AF: 0.162

Gnomad AMI AF: 0.109

Gnomad AMR AF: 0.154

Gnomad ASJ AF: 0.165

Gnomad EAS AF: 0.0285

Gnomad SAS AF: 0.150

Gnomad FIN AF: 0.194

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.181

Gnomad OTH AF: 0.143

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

GnomAD4 genome AF: 0.166 AC: 25310 AN: 152152 Hom.: 2139 Cov.: 32 AF XY: 0.165 AC XY: 12261 AN XY: 74408

Gnomad4 AFR AF: 0.162

Gnomad4 AMR AF: 0.154

Gnomad4 ASJ AF: 0.165

Gnomad4 EAS AF: 0.0284

Gnomad4 SAS AF: 0.151

Gnomad4 FIN AF: 0.194

Gnomad4 NFE AF: 0.181

Gnomad4 OTH AF: 0.142

Alfa AF: 0.174 Hom.: 1327

Bravo AF: 0.162

Asia WGS AF: 0.0940 AC: 328 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.20
DANN	Benign	0.50

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1544295; hg19: chr13-43498689;