11-18348800-C-T

Position:

• chr11-18348800-C-T

Variant summary

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

The NM_005316.4(GTF2H1):​c.1053+881C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.139 in 152,092 control chromosomes in the GnomAD database, including 1,567 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 0.14 (1567 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: GTF2H1 NM_005316.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.573

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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.184 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GTF2H1	NM_005316.4	c.1053+881C>T		intron_variant		ENST00000265963.9	NP_005307.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GTF2H1	ENST00000265963.9	c.1053+881C>T		intron_variant		1	NM_005316.4	ENSP00000265963	P1

Frequencies

GnomAD3 genomes AF: 0.139 AC: 21055 AN: 151974 Hom.: 1564 Cov.: 32

Gnomad AFR AF: 0.187

Gnomad AMI AF: 0.0549

Gnomad AMR AF: 0.155

Gnomad ASJ AF: 0.123

Gnomad EAS AF: 0.119

Gnomad SAS AF: 0.130

Gnomad FIN AF: 0.176

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.103

Gnomad OTH AF: 0.150

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.139 AC: 21067 AN: 152092 Hom.: 1567 Cov.: 32 AF XY: 0.141 AC XY: 10512 AN XY: 74316

Gnomad4 AFR AF: 0.187

Gnomad4 AMR AF: 0.155

Gnomad4 ASJ AF: 0.123

Gnomad4 EAS AF: 0.119

Gnomad4 SAS AF: 0.129

Gnomad4 FIN AF: 0.176

Gnomad4 NFE AF: 0.103

Gnomad4 OTH AF: 0.149

Alfa AF: 0.135 Hom.: 264

Bravo AF: 0.139

Asia WGS AF: 0.141 AC: 490 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	2.0
DANN	Benign	0.59

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: rs4237721; hg19: chr11-18370347;