11-18329351-C-G

Position:

• chr11-18329351-C-G

Variant summary

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

The NM_005316.4(GTF2H1):​c.-15-3709C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.645 in 151,984 control chromosomes in the GnomAD database, including 32,656 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 0.65 (32656 hom., cov: 31)
• Consequence: GTF2H1 NM_005316.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.684

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=-0.88).
• 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.-15-3709C>G		intron_variant		ENST00000265963.9	NP_005307.1
GTF2H1	NM_001142307.2	c.-16+3198C>G		intron_variant			NP_001135779.1
GTF2H1	XM_006718208.4	c.-15-3709C>G		intron_variant			XP_006718271.1
GTF2H1	XM_024448457.2	c.-16+3198C>G		intron_variant			XP_024304225.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GTF2H1	ENST00000265963.9	c.-15-3709C>G		intron_variant		1	NM_005316.4	ENSP00000265963.4

Frequencies

GnomAD3 genomes AF: 0.645 AC: 98025 AN: 151864 Hom.: 32650 Cov.: 31

Gnomad AFR AF: 0.492

Gnomad AMI AF: 0.760

Gnomad AMR AF: 0.718

Gnomad ASJ AF: 0.592

Gnomad EAS AF: 0.964

Gnomad SAS AF: 0.665

Gnomad FIN AF: 0.719

Gnomad MID AF: 0.580

Gnomad NFE AF: 0.687

Gnomad OTH AF: 0.649

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

GnomAD4 genome AF: 0.645 AC: 98072 AN: 151984 Hom.: 32656 Cov.: 31 AF XY: 0.650 AC XY: 48301 AN XY: 74262

Gnomad4 AFR AF: 0.492

Gnomad4 AMR AF: 0.718

Gnomad4 ASJ AF: 0.592

Gnomad4 EAS AF: 0.964

Gnomad4 SAS AF: 0.666

Gnomad4 FIN AF: 0.719

Gnomad4 NFE AF: 0.687

Gnomad4 OTH AF: 0.652

Alfa AF: 0.536 Hom.: 1588

Bravo AF: 0.642

Asia WGS AF: 0.809 AC: 2808 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	8.2
DANN	Benign	0.70

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: rs4150550; hg19: chr11-18350898;