11-18322517-T-C

Position:

• chr11-18322517-T-C

Variant summary

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

The ENST00000453096(GTF2H1):​c.-446T>C variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.417 in 152,148 control chromosomes in the GnomAD database, including 15,517 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 0.42 (15491 hom., cov: 31)
  • Exomes 𝑓: 0.59 (26 hom.)
• Consequence: GTF2H1 ENST00000453096 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.519

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=-0.52).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.569 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GTF2H1	NM_005316.4	c.-239T>C		upstream_gene_variant		ENST00000265963.9	NP_005307.1
GTF2H1	NM_001142307.2	c.-446T>C		upstream_gene_variant			NP_001135779.1
GTF2H1	XM_006718208.4	c.-300T>C		upstream_gene_variant			XP_006718271.1
GTF2H1	XM_024448457.2	c.-507T>C		upstream_gene_variant			XP_024304225.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GTF2H1	ENST00000265963.9	c.-239T>C		upstream_gene_variant		1	NM_005316.4	ENSP00000265963.4

Frequencies

GnomAD3 genomes AF: 0.417 AC: 63319 AN: 151892 Hom.: 15491 Cov.: 31

Gnomad AFR AF: 0.148

Gnomad AMI AF: 0.646

Gnomad AMR AF: 0.481

Gnomad ASJ AF: 0.367

Gnomad EAS AF: 0.587

Gnomad SAS AF: 0.403

Gnomad FIN AF: 0.517

Gnomad MID AF: 0.318

Gnomad NFE AF: 0.539

Gnomad OTH AF: 0.405

GnomAD4 exome AF: 0.587 AC: 81 AN: 138 Hom.: 26 Cov.: 0 AF XY: 0.587 AC XY: 61 AN XY: 104

Gnomad4 AMR exome AF: 1.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.667

Gnomad4 FIN exome AF: 1.00

Gnomad4 NFE exome AF: 0.574

Gnomad4 OTH exome AF: 0.750

GnomAD4 genome AF: 0.417 AC: 63326 AN: 152010 Hom.: 15491 Cov.: 31 AF XY: 0.417 AC XY: 30987 AN XY: 74292

Gnomad4 AFR AF: 0.148

Gnomad4 AMR AF: 0.481

Gnomad4 ASJ AF: 0.367

Gnomad4 EAS AF: 0.587

Gnomad4 SAS AF: 0.404

Gnomad4 FIN AF: 0.517

Gnomad4 NFE AF: 0.539

Gnomad4 OTH AF: 0.404

Alfa AF: 0.492 Hom.: 28662

Bravo AF: 0.404

Asia WGS AF: 0.456 AC: 1585 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	9.9
DANN	Benign	0.83

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: rs3802967; hg19: chr11-18344064;