rs4150563

chr11-18333555-T-G

Variant summary

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

The NM_005316.4(GTF2H1):c.154+327T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.157 in 174,586 control chromosomes in the GnomAD database, including 2,845 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 0.15 (2326 hom., cov: 33)
  • Exomes 𝑓: 0.19 (519 hom.)
• Consequence: GTF2H1 NM_005316.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.07

Genes affected

GTF2H1 (HGNC:4655): (general transcription factor IIH subunit 1) Enables thyroid hormone receptor binding activity. Involved in positive regulation of transcription, DNA-templated and transcription by RNA polymerase II. Located in nucleoplasm. Part of transcription factor TFIIH core complex and transcription factor TFIIH holo 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=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.211 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GTF2H1	NM_005316.4	c.154+327T>G		intron_variant		ENST00000265963.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GTF2H1	ENST00000265963.9	c.154+327T>G		intron_variant		1	NM_005316.4	P1

Frequencies

GnomAD3 genomes AF: 0.152 AC: 23151 AN: 152126 Hom.: 2324 Cov.: 33

Gnomad AFR AF: 0.0383

Gnomad AMI AF: 0.207

Gnomad AMR AF: 0.142

Gnomad ASJ AF: 0.0748

Gnomad EAS AF: 0.0391

Gnomad SAS AF: 0.115

Gnomad FIN AF: 0.310

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.214

Gnomad OTH AF: 0.140

GnomAD4 exome AF: 0.190 AC: 4237 AN: 22342 Hom.: 519 Cov.: 0 AF XY: 0.185 AC XY: 2116 AN XY: 11416

Gnomad4 AFR exome AF: 0.0270

Gnomad4 AMR exome AF: 0.118

Gnomad4 ASJ exome AF: 0.0839

Gnomad4 EAS exome AF: 0.0319

Gnomad4 SAS exome AF: 0.116

Gnomad4 FIN exome AF: 0.324

Gnomad4 NFE exome AF: 0.221

Gnomad4 OTH exome AF: 0.191

GnomAD4 genome AF: 0.152 AC: 23151 AN: 152244 Hom.: 2326 Cov.: 33 AF XY: 0.156 AC XY: 11621 AN XY: 74432

Gnomad4 AFR AF: 0.0382

Gnomad4 AMR AF: 0.142

Gnomad4 ASJ AF: 0.0748

Gnomad4 EAS AF: 0.0391

Gnomad4 SAS AF: 0.116

Gnomad4 FIN AF: 0.310

Gnomad4 NFE AF: 0.214

Gnomad4 OTH AF: 0.139

Alfa AF: 0.188 Hom.: 1540

Bravo AF: 0.133

Asia WGS AF: 0.0740 AC: 255 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	7.6
Dann	Benign	0.72

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: rs4150563; hg19: chr11-18355102;