rs12870438

chr13-42906069-G-A

Variant summary

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

The NM_033255.5(EPSTI1):c.742-5686C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.271 in 152,148 control chromosomes in the GnomAD database, including 7,054 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 0.27 (7054 hom., cov: 32)
• Consequence: EPSTI1 NM_033255.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.504

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]

LOC124903165 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.381 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EPSTI1	NM_033255.5	c.742-5686C>T		intron_variant		ENST00000313624.12
LOC124903165	XR_007063772.1	n.116+8417G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EPSTI1	ENST00000313624.12	c.742-5686C>T		intron_variant		1	NM_033255.5	P4

Frequencies

GnomAD3 genomes AF: 0.272 AC: 41294 AN: 152030 Hom.: 7053 Cov.: 32

Gnomad AFR AF: 0.0787

Gnomad AMI AF: 0.417

Gnomad AMR AF: 0.253

Gnomad ASJ AF: 0.422

Gnomad EAS AF: 0.153

Gnomad SAS AF: 0.163

Gnomad FIN AF: 0.360

Gnomad MID AF: 0.366

Gnomad NFE AF: 0.385

Gnomad OTH AF: 0.309

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

GnomAD4 genome AF: 0.271 AC: 41288 AN: 152148 Hom.: 7054 Cov.: 32 AF XY: 0.269 AC XY: 19971 AN XY: 74376

Gnomad4 AFR AF: 0.0785

Gnomad4 AMR AF: 0.253

Gnomad4 ASJ AF: 0.422

Gnomad4 EAS AF: 0.153

Gnomad4 SAS AF: 0.164

Gnomad4 FIN AF: 0.360

Gnomad4 NFE AF: 0.385

Gnomad4 OTH AF: 0.307

Alfa AF: 0.310 Hom.: 1423

Bravo AF: 0.259

Asia WGS AF: 0.168 AC: 585 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	2.3
Dann	Benign	0.52

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: rs12870438; hg19: chr13-43480205; COSMIC: COSV58048398;