rs1544295

Variant names:

• chr13-42924553-C-T
• rs1544295
• NM_033255.5:c.657+1783G>A

Variant summary

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

The NM_001002264.4(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_001002264.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.07
• Publications: 4 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001002264.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EPSTI1	NM_033255.5	MANE Select	c.657+1783G>A		intron	N/A	NP_150280.1
	EPSTI1	NM_001002264.4		c.657+1783G>A		intron	N/A	NP_001002264.1
	EPSTI1	NM_001330543.2		c.657+1783G>A		intron	N/A	NP_001317472.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EPSTI1	ENST00000313624.12	TSL:1 MANE Select	c.657+1783G>A		intron	N/A	ENSP00000318643.7
	EPSTI1	ENST00000313640.11	TSL:1	c.657+1783G>A		intron	N/A	ENSP00000318982.7
	EPSTI1	ENST00000398762.7	TSL:5	c.657+1783G>A		intron	N/A	ENSP00000381746.3

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

African (AFR) AF: 0.162 AC: 6740 AN: 41504

American (AMR) AF: 0.154 AC: 2357 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.165 AC: 574 AN: 3472

East Asian (EAS) AF: 0.0284 AC: 147 AN: 5180

South Asian (SAS) AF: 0.151 AC: 726 AN: 4816

European-Finnish (FIN) AF: 0.194 AC: 2057 AN: 10590

Middle Eastern (MID) AF: 0.0782 AC: 23 AN: 294

European-Non Finnish (NFE) AF: 0.181 AC: 12288 AN: 67990

Other (OTH) AF: 0.142 AC: 299 AN: 2110

Alfa AF: 0.173 Hom.: 1442

Bravo AF: 0.162

Asia WGS AF: 0.0940 AC: 328 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.20
DANN	Benign	0.50
PhyloP100		-1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1544295; hg19: chr13-43498689;