rs1264308

chr6-30912210-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001517.5(GTF2H4):c.958+64C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.115 in 1,603,026 control chromosomes in the GnomAD database, including 12,997 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 0.075 (609 hom., cov: 31)
  • Exomes 𝑓: 0.12 (12388 hom.)
• Consequence: GTF2H4 NM_001517.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0660

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.117 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GTF2H4	NM_001517.5	c.958+64C>T		intron_variant		ENST00000259895.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GTF2H4	ENST00000259895.9	c.958+64C>T		intron_variant		1	NM_001517.5	P1

Frequencies

GnomAD3 genomes AF: 0.0745 AC: 11326 AN: 151968 Hom.: 609 Cov.: 31

Gnomad AFR AF: 0.0326

Gnomad AMI AF: 0.146

Gnomad AMR AF: 0.0294

Gnomad ASJ AF: 0.0444

Gnomad EAS AF: 0.00405

Gnomad SAS AF: 0.0536

Gnomad FIN AF: 0.0703

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.119

Gnomad OTH AF: 0.0533

GnomAD4 exome AF: 0.119 AC: 173109 AN: 1450940 Hom.: 12388 Cov.: 32 AF XY: 0.118 AC XY: 85044 AN XY: 721056

Gnomad4 AFR exome AF: 0.0328

Gnomad4 AMR exome AF: 0.0224

Gnomad4 ASJ exome AF: 0.0441

Gnomad4 EAS exome AF: 0.00104

Gnomad4 SAS exome AF: 0.0695

Gnomad4 FIN exome AF: 0.0746

Gnomad4 NFE exome AF: 0.139

Gnomad4 OTH exome AF: 0.102

GnomAD4 genome AF: 0.0746 AC: 11351 AN: 152086 Hom.: 609 Cov.: 31 AF XY: 0.0695 AC XY: 5167 AN XY: 74328

Gnomad4 AFR AF: 0.0331

Gnomad4 AMR AF: 0.0293

Gnomad4 ASJ AF: 0.0444

Gnomad4 EAS AF: 0.00406

Gnomad4 SAS AF: 0.0547

Gnomad4 FIN AF: 0.0703

Gnomad4 NFE AF: 0.119

Gnomad4 OTH AF: 0.0527

Alfa AF: 0.107 Hom.: 1481

Bravo AF: 0.0694

Asia WGS AF: 0.0210 AC: 73 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	6.2
Dann	Benign	0.54

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs1264308; hg19: chr6-30879987;