8-30579335-C-T

Variant names:

• chr8-30579335-C-T
• rs10503871
• NM_002095.6:c.760-298G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_002095.6(GTF2E2):​c.760-298G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.447 in 152,034 control chromosomes in the GnomAD database, including 15,181 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.45 (15181 hom., cov: 32)
• Consequence: GTF2E2 NM_002095.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.322
• Publications: 7 publications found

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]

GTF2E2 Gene-Disease associations (from GenCC):

• trichothiodystrophy 6, nonphotosensitive

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Genomics England PanelApp, G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
• trichothiodystrophy

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 8-30579335-C-T is Benign according to our data. Variant chr8-30579335-C-T is described in ClinVar as Benign. ClinVar VariationId is 1261800.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.466 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GTF2E2	NM_002095.6	c.760-298G>A		intron_variant	Intron 7 of 7	ENST00000355904.9	NP_002086.1
GTF2E2	XM_017013363.2	c.760-298G>A		intron_variant	Intron 7 of 7		XP_016868852.1
GTF2E2	XM_017013364.2	c.760-298G>A		intron_variant	Intron 7 of 7		XP_016868853.1
GTF2E2	XM_024447138.2	c.760-298G>A		intron_variant	Intron 7 of 7		XP_024302906.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GTF2E2	ENST00000355904.9	c.760-298G>A		intron_variant	Intron 7 of 7	1	NM_002095.6	ENSP00000348168.4

Frequencies

GnomAD3 genomes AF: 0.447 AC: 67932 AN: 151916 Hom.: 15167 Cov.: 32

Gnomad AFR AF: 0.421

Gnomad AMI AF: 0.399

Gnomad AMR AF: 0.401

Gnomad ASJ AF: 0.438

Gnomad EAS AF: 0.442

Gnomad SAS AF: 0.358

Gnomad FIN AF: 0.512

Gnomad MID AF: 0.541

Gnomad NFE AF: 0.470

Gnomad OTH AF: 0.469

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

GnomAD4 genome AF: 0.447 AC: 67972 AN: 152034 Hom.: 15181 Cov.: 32 AF XY: 0.447 AC XY: 33231 AN XY: 74284

African (AFR) AF: 0.421 AC: 17464 AN: 41482

American (AMR) AF: 0.400 AC: 6111 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.438 AC: 1518 AN: 3468

East Asian (EAS) AF: 0.443 AC: 2288 AN: 5166

South Asian (SAS) AF: 0.359 AC: 1729 AN: 4810

European-Finnish (FIN) AF: 0.512 AC: 5407 AN: 10562

Middle Eastern (MID) AF: 0.551 AC: 162 AN: 294

European-Non Finnish (NFE) AF: 0.470 AC: 31944 AN: 67958

Other (OTH) AF: 0.467 AC: 986 AN: 2112

Alfa AF: 0.452 Hom.: 5289

Bravo AF: 0.439

Asia WGS AF: 0.389 AC: 1352 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	5.9
DANN	Benign	0.72
PhyloP100		0.32
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10503871; hg19: chr8-30436852;