chr6-30912980-G-A

Position:

• chr6-30912980-G-A

Variant summary

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

The NM_001517.5(GTF2H4):​c.1090-130G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.321 in 797,246 control chromosomes in the GnomAD database, including 43,954 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 0.28 (6815 hom., cov: 31)
  • Exomes 𝑓: 0.33 (37139 hom.)
• Consequence: GTF2H4 NM_001517.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.302

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.358 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GTF2H4	NM_001517.5	c.1090-130G>A		intron_variant		ENST00000259895.9	NP_001508.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GTF2H4	ENST00000259895.9	c.1090-130G>A		intron_variant		1	NM_001517.5	ENSP00000259895.4

Frequencies

GnomAD3 genomes AF: 0.280 AC: 42504 AN: 151940 Hom.: 6818 Cov.: 31

Gnomad AFR AF: 0.125

Gnomad AMI AF: 0.294

Gnomad AMR AF: 0.242

Gnomad ASJ AF: 0.401

Gnomad EAS AF: 0.253

Gnomad SAS AF: 0.264

Gnomad FIN AF: 0.392

Gnomad MID AF: 0.377

Gnomad NFE AF: 0.362

Gnomad OTH AF: 0.281

GnomAD4 exome AF: 0.330 AC: 213098 AN: 645188 Hom.: 37139 AF XY: 0.329 AC XY: 109936 AN XY: 333734

Gnomad4 AFR exome AF: 0.117

Gnomad4 AMR exome AF: 0.218

Gnomad4 ASJ exome AF: 0.371

Gnomad4 EAS exome AF: 0.232

Gnomad4 SAS exome AF: 0.272

Gnomad4 FIN exome AF: 0.382

Gnomad4 NFE exome AF: 0.355

Gnomad4 OTH exome AF: 0.308

GnomAD4 genome AF: 0.280 AC: 42514 AN: 152058 Hom.: 6815 Cov.: 31 AF XY: 0.281 AC XY: 20863 AN XY: 74314

Gnomad4 AFR AF: 0.125

Gnomad4 AMR AF: 0.242

Gnomad4 ASJ AF: 0.401

Gnomad4 EAS AF: 0.253

Gnomad4 SAS AF: 0.263

Gnomad4 FIN AF: 0.392

Gnomad4 NFE AF: 0.362

Gnomad4 OTH AF: 0.279

Alfa AF: 0.344 Hom.: 5439

Bravo AF: 0.263

Asia WGS AF: 0.207 AC: 725 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	15
DANN	Benign	0.77

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: rs1264307; hg19: chr6-30880757;