chr11-18363391-A-G

Variant names:

• chr11-18363391-A-G
• rs9783347
• NM_005316.4:c.1561-2392A>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.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
• Publications: 14 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=-0.64).
• 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 rank	MANE	Protein	UniProt
GTF2H1	NM_005316.4	c.1561-2392A>G		intron_variant	Intron 14 of 14	ENST00000265963.9	NP_005307.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GTF2H1	ENST00000265963.9	c.1561-2392A>G		intron_variant	Intron 14 of 14	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

African (AFR) AF: 0.438 AC: 18136 AN: 41444

American (AMR) AF: 0.696 AC: 10623 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.590 AC: 2045 AN: 3468

East Asian (EAS) AF: 0.964 AC: 4982 AN: 5168

South Asian (SAS) AF: 0.665 AC: 3195 AN: 4802

European-Finnish (FIN) AF: 0.718 AC: 7558 AN: 10520

Middle Eastern (MID) AF: 0.551 AC: 161 AN: 292

European-Non Finnish (NFE) AF: 0.683 AC: 46453 AN: 67974

Other (OTH) AF: 0.629 AC: 1324 AN: 2106

Alfa AF: 0.628 Hom.: 16238

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
PhyloP100		0.35
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: rs9783347; hg19: chr11-18384938;