11-18353986-G-A

Position:

• chr11-18353986-G-A

Variant summary

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

The NM_005316.4(GTF2H1):​c.1260+1540G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.865 in 152,276 control chromosomes in the GnomAD database, including 57,337 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 0.87 (57337 hom., cov: 33)
• Consequence: GTF2H1 NM_005316.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0760

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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.946 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GTF2H1	NM_005316.4	c.1260+1540G>A		intron_variant		ENST00000265963.9	NP_005307.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GTF2H1	ENST00000265963.9	c.1260+1540G>A		intron_variant		1	NM_005316.4	ENSP00000265963	P1

Frequencies

GnomAD3 genomes AF: 0.865 AC: 131616 AN: 152158 Hom.: 57282 Cov.: 33

Gnomad AFR AF: 0.950

Gnomad AMI AF: 0.818

Gnomad AMR AF: 0.835

Gnomad ASJ AF: 0.725

Gnomad EAS AF: 0.968

Gnomad SAS AF: 0.793

Gnomad FIN AF: 0.867

Gnomad MID AF: 0.703

Gnomad NFE AF: 0.826

Gnomad OTH AF: 0.830

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

GnomAD4 genome AF: 0.865 AC: 131732 AN: 152276 Hom.: 57337 Cov.: 33 AF XY: 0.865 AC XY: 64358 AN XY: 74440

Gnomad4 AFR AF: 0.950

Gnomad4 AMR AF: 0.835

Gnomad4 ASJ AF: 0.725

Gnomad4 EAS AF: 0.968

Gnomad4 SAS AF: 0.793

Gnomad4 FIN AF: 0.867

Gnomad4 NFE AF: 0.826

Gnomad4 OTH AF: 0.832

Alfa AF: 0.827 Hom.: 31868

Bravo AF: 0.868

Asia WGS AF: 0.916 AC: 3180 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.33
DANN	Benign	0.54

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: rs7103375; hg19: chr11-18375533;