8-30580122-C-T

Position:

• chr8-30580122-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_002095.6(GTF2E2):​c.759+159G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.216 in 152,064 control chromosomes in the GnomAD database, including 4,040 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.22 (4040 hom., cov: 32)
• Consequence: GTF2E2 NM_002095.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.361

Genes affected

GTF2E2 (HGNC:4651): (general transcription factor IIE subunit 2) The general transcription factor IIE (TFIIE) is part of the RNA polymerase II transcription initiation complex, recruiting TFIIH and being essential for promoter clearance by RNA polymerase II. TFIIE is a heterodimer (and sometimes heterotetramer) of alpha and beta subunits. The protein encoded by this gene represents the beta subunit of TFIIE. [provided by RefSeq, Jan 2017]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 8-30580122-C-T is Benign according to our data. Variant chr8-30580122-C-T is described in ClinVar as [Benign]. Clinvar id is 1288094.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.368 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GTF2E2	NM_002095.6	c.759+159G>A		intron_variant		ENST00000355904.9	NP_002086.1
GTF2E2	XM_017013363.2	c.759+159G>A		intron_variant			XP_016868852.1
GTF2E2	XM_017013364.2	c.759+159G>A		intron_variant			XP_016868853.1
GTF2E2	XM_024447138.2	c.759+159G>A		intron_variant			XP_024302906.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GTF2E2	ENST00000355904.9	c.759+159G>A		intron_variant		1	NM_002095.6	ENSP00000348168	P1

Frequencies

GnomAD3 genomes AF: 0.216 AC: 32772 AN: 151948 Hom.: 4040 Cov.: 32

Gnomad AFR AF: 0.0994

Gnomad AMI AF: 0.409

Gnomad AMR AF: 0.190

Gnomad ASJ AF: 0.355

Gnomad EAS AF: 0.108

Gnomad SAS AF: 0.383

Gnomad FIN AF: 0.286

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.268

Gnomad OTH AF: 0.202

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

GnomAD4 genome AF: 0.216 AC: 32774 AN: 152064 Hom.: 4040 Cov.: 32 AF XY: 0.217 AC XY: 16161 AN XY: 74312

Gnomad4 AFR AF: 0.0993

Gnomad4 AMR AF: 0.190

Gnomad4 ASJ AF: 0.355

Gnomad4 EAS AF: 0.108

Gnomad4 SAS AF: 0.382

Gnomad4 FIN AF: 0.286

Gnomad4 NFE AF: 0.268

Gnomad4 OTH AF: 0.204

Alfa AF: 0.132 Hom.: 254

Bravo AF: 0.201

Asia WGS AF: 0.244 AC: 846 AN: 3478

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

GeneDx

Nov 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.5
DANN	Benign	0.62

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: rs62505275; hg19: chr8-30437639; COSMIC: COSV63479194; COSMIC: COSV63479194;