chr11-18363391-A-G

Position:

• chr11-18363391-A-G

Variant summary

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

The NM_005316.4(GTF2H1):​c.1561-2392A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.626 in 151,944 control chromosomes in the GnomAD database, including 31,202 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 0.63 (31202 hom., cov: 31)
• Consequence: GTF2H1 NM_005316.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.347

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=-0.64).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.942 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GTF2H1	NM_005316.4	c.1561-2392A>G		intron_variant		ENST00000265963.9	NP_005307.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GTF2H1	ENST00000265963.9	c.1561-2392A>G		intron_variant		1	NM_005316.4	ENSP00000265963.4

Frequencies

GnomAD3 genomes AF: 0.627 AC: 95126 AN: 151826 Hom.: 31195 Cov.: 31

Gnomad AFR AF: 0.438

Gnomad AMI AF: 0.758

Gnomad AMR AF: 0.696

Gnomad ASJ AF: 0.590

Gnomad EAS AF: 0.964

Gnomad SAS AF: 0.665

Gnomad FIN AF: 0.718

Gnomad MID AF: 0.564

Gnomad NFE AF: 0.683

Gnomad OTH AF: 0.626

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.626 AC: 95168 AN: 151944 Hom.: 31202 Cov.: 31 AF XY: 0.632 AC XY: 46883 AN XY: 74220

Gnomad4 AFR AF: 0.438

Gnomad4 AMR AF: 0.696

Gnomad4 ASJ AF: 0.590

Gnomad4 EAS AF: 0.964

Gnomad4 SAS AF: 0.665

Gnomad4 FIN AF: 0.718

Gnomad4 NFE AF: 0.683

Gnomad4 OTH AF: 0.629

Alfa AF: 0.654 Hom.: 7847

Bravo AF: 0.621

Asia WGS AF: 0.804 AC: 2793 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	9.0
DANN	Benign	0.84

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: rs9783347; hg19: chr11-18384938;