13-42964145-G-GA

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_033255.5(EPSTI1):c.332-7_332-6insT variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00464 in 1,589,758 control chromosomes in the GnomAD database, including 237 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.023 (139 hom., cov: 32)
  • Exomes 𝑓: 0.0027 (98 hom.)
• Consequence: EPSTI1 NM_033255.5 splice_region, splice_polypyrimidine_tract, intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.206

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 -10 ACMG points.

• BP6: Variant 13-42964145-G-GA is Benign according to our data. Variant chr13-42964145-G-GA is described in ClinVar as [Benign]. Clinvar id is 784269.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0797 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EPSTI1	NM_033255.5	c.332-7_332-6insT		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000313624.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EPSTI1	ENST00000313624.12	c.332-7_332-6insT		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_033255.5	P4

Frequencies

GnomAD3 genomes AF: 0.0234 AC: 3516 AN: 150084 Hom.: 137 Cov.: 32

Gnomad AFR AF: 0.0820

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00728

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000631

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000341

Gnomad OTH AF: 0.0146

GnomAD3 exomes AF: 0.00688 AC: 1540 AN: 223988 Hom.: 45 AF XY: 0.00492 AC XY: 597 AN XY: 121344

Gnomad AFR exome AF: 0.0849

Gnomad AMR exome AF: 0.00521

Gnomad ASJ exome AF: 0.000109

Gnomad EAS exome AF: 0.000126

Gnomad SAS exome AF: 0.000556

Gnomad FIN exome AF: 0.000353

Gnomad NFE exome AF: 0.000695

Gnomad OTH exome AF: 0.00526

GnomAD4 exome AF: 0.00268 AC: 3851 AN: 1439560 Hom.: 98 Cov.: 29 AF XY: 0.00235 AC XY: 1681 AN XY: 716180

Gnomad4 AFR exome AF: 0.0832

Gnomad4 AMR exome AF: 0.00469

Gnomad4 ASJ exome AF: 0.000195

Gnomad4 EAS exome AF: 0.0000770

Gnomad4 SAS exome AF: 0.000502

Gnomad4 FIN exome AF: 0.000286

Gnomad4 NFE exome AF: 0.000472

Gnomad4 OTH exome AF: 0.00547

GnomAD4 genome AF: 0.0235 AC: 3526 AN: 150198 Hom.: 139 Cov.: 32 AF XY: 0.0229 AC XY: 1681 AN XY: 73288

Gnomad4 AFR AF: 0.0820

Gnomad4 AMR AF: 0.00727

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000631

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000341

Gnomad4 OTH AF: 0.0145

Bravo AF: 0.0257

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Apr 10, 2018

- -

Computational scores

Source: dbNSFP v4.3

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: rs148862630; hg19: chr13-43538281;