rs4150606

Positions:

• chr11-18342022-C-A
• chr11-18342022-C-T

Variant summary

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

The NM_005316.4(GTF2H1):​c.837+415C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.461 in 154,648 control chromosomes in the GnomAD database, including 18,909 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 0.46 (18504 hom., cov: 30)
  • Exomes 𝑓: 0.51 (405 hom.)
• Consequence: GTF2H1 NM_005316.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0810

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]

GTF2H1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.827 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GTF2H1	NM_005316.4	c.837+415C>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.837+415C>A		intron_variant		1	NM_005316.4	ENSP00000265963.4

Frequencies

GnomAD3 genomes AF: 0.461 AC: 69886 AN: 151728 Hom.: 18501 Cov.: 30

Gnomad AFR AF: 0.196

Gnomad AMI AF: 0.671

Gnomad AMR AF: 0.523

Gnomad ASJ AF: 0.425

Gnomad EAS AF: 0.848

Gnomad SAS AF: 0.530

Gnomad FIN AF: 0.525

Gnomad MID AF: 0.358

Gnomad NFE AF: 0.564

Gnomad OTH AF: 0.441

GnomAD4 exome AF: 0.508 AC: 1424 AN: 2802 Hom.: 405 AF XY: 0.518 AC XY: 796 AN XY: 1536

Gnomad4 AFR exome AF: 0.200

Gnomad4 AMR exome AF: 0.486

Gnomad4 ASJ exome AF: 0.321

Gnomad4 EAS exome AF: 0.722

Gnomad4 SAS exome AF: 0.466

Gnomad4 FIN exome AF: 0.515

Gnomad4 NFE exome AF: 0.521

Gnomad4 OTH exome AF: 0.418

GnomAD4 genome AF: 0.460 AC: 69910 AN: 151846 Hom.: 18504 Cov.: 30 AF XY: 0.463 AC XY: 34372 AN XY: 74168

Gnomad4 AFR AF: 0.196

Gnomad4 AMR AF: 0.523

Gnomad4 ASJ AF: 0.425

Gnomad4 EAS AF: 0.847

Gnomad4 SAS AF: 0.531

Gnomad4 FIN AF: 0.525

Gnomad4 NFE AF: 0.564

Gnomad4 OTH AF: 0.446

Alfa AF: 0.517 Hom.: 19530

Bravo AF: 0.453

Asia WGS AF: 0.656 AC: 2279 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.60
DANN	Benign	0.29

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: rs4150606; hg19: chr11-18363569;