11-18329351-C-G

Variant names:

• chr11-18329351-C-G
• rs4150550
• NM_005316.4:c.-15-3709C>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 10 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
GTF2H1	NM_005316.4	c.-15-3709C>G		intron_variant	Intron 1 of 14	ENST00000265963.9	NP_005307.1
GTF2H1	NM_001142307.2	c.-16+3198C>G		intron_variant	Intron 2 of 15		NP_001135779.1
GTF2H1	XM_006718208.4	c.-15-3709C>G		intron_variant	Intron 2 of 15		XP_006718271.1
GTF2H1	XM_024448457.2	c.-16+3198C>G		intron_variant	Intron 3 of 16		XP_024304225.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GTF2H1	ENST00000265963.9	c.-15-3709C>G		intron_variant	Intron 1 of 14	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

African (AFR) AF: 0.492 AC: 20389 AN: 41440

American (AMR) AF: 0.718 AC: 10962 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.592 AC: 2053 AN: 3468

East Asian (EAS) AF: 0.964 AC: 4993 AN: 5180

South Asian (SAS) AF: 0.666 AC: 3206 AN: 4812

European-Finnish (FIN) AF: 0.719 AC: 7578 AN: 10538

Middle Eastern (MID) AF: 0.568 AC: 166 AN: 292

European-Non Finnish (NFE) AF: 0.687 AC: 46661 AN: 67966

Other (OTH) AF: 0.652 AC: 1371 AN: 2104

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
PhyloP100		-0.68
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4150550; hg19: chr11-18350898;