Variant 6-30912434-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_001517.5(GTF2H4):c.1065C>T(p.Ile355Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00429 in 1,612,688 control chromosomes in the GnomAD database, including 25 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0049 ( 3 hom., cov: 32)

Exomes 𝑓: 0.0042 ( 22 hom. )

Consequence

GTF2H4
NM_001517.5 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.18

Variant links:

Genes affected

GTF2H4 (HGNC:4658): (general transcription factor IIH subunit 4) Enables RNA polymerase II general transcription initiation factor activity. Involved in transcription by RNA polymerase II. Located in nuclear speck. Part of core TFIIH complex portion of holo TFIIH complex and transcription factor TFIID complex. [provided by Alliance of Genome Resources, Apr 2022]

GTF2H4 links:

GTF2H4 (HGNC:):

GTF2H4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.55).

BP6

Variant 6-30912434-C-T is Benign according to our data. Variant chr6-30912434-C-T is described in ClinVar as [Benign]. Clinvar id is 789744.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-1.18 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GTF2H4	NM_001517.5 linkuse as main transcript	c.1065C>T	p.Ile355Ile	synonymous_variant	11/14	ENST00000259895.9	NP_001508.1	Q92759-1A0A1U9X7S4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GTF2H4	ENST00000259895.9 linkuse as main transcript	c.1065C>T	p.Ile355Ile	synonymous_variant	11/14	1	NM_001517.5	ENSP00000259895.4		Q92759-1

Frequencies

GnomAD3 genomes

AF:

0.00488

AC:

743

AN:

152146

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00505

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00583

Gnomad ASJ

AF:

0.0147

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00103

Gnomad FIN

AF:

0.00132

Gnomad MID

AF:

0.0285

Gnomad NFE

AF:

0.00504

Gnomad OTH

AF:

0.0105

GnomAD3 exomes

AF:

0.00427

AC:

1050

AN:

245986

Hom.:

AF XY:

0.00433

AC XY:

580

AN XY:

134066

show subpopulations

Gnomad AFR exome

AF:

0.00516

Gnomad AMR exome

AF:

0.00418

Gnomad ASJ exome

AF:

0.0190

Gnomad EAS exome

AF:

0.000164

Gnomad SAS exome

AF:

0.00181

Gnomad FIN exome

AF:

0.00191

Gnomad NFE exome

AF:

0.00452

Gnomad OTH exome

AF:

0.00693

GnomAD4 exome

AF:

0.00423

AC:

6175

AN:

1460424

Hom.:

Cov.:

AF XY:

0.00415

AC XY:

3013

AN XY:

726536

show subpopulations

Gnomad4 AFR exome

AF:

0.00597

Gnomad4 AMR exome

AF:

0.00508

Gnomad4 ASJ exome

AF:

0.0167

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00176

Gnomad4 FIN exome

AF:

0.00192

Gnomad4 NFE exome

AF:

0.00421

Gnomad4 OTH exome

AF:

0.00519

GnomAD4 genome

AF:

0.00486

AC:

740

AN:

152264

Hom.:

Cov.:

AF XY:

0.00482

AC XY:

359

AN XY:

74454

show subpopulations

Gnomad4 AFR

AF:

0.00503

Gnomad4 AMR

AF:

0.00582

Gnomad4 ASJ

AF:

0.0147

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00104

Gnomad4 FIN

AF:

0.00132

Gnomad4 NFE

AF:

0.00503

Gnomad4 OTH

AF:

0.0104

Alfa

AF:

0.00557

Hom.:

Bravo

AF:

0.00504

Asia WGS

AF:

0.00173

AC:

AN:

3478

EpiCase

AF:

0.00507

EpiControl

AF:

0.00522

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jun 22, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.55

CADD

Benign

1.3

DANN

Benign

0.75

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over