rs4596

Positions:

• chr11-18366581-G-C
• chr11-18366581-G-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_005316.4(GTF2H1):​c.*712G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.417 in 152,472 control chromosomes in the GnomAD database, including 15,557 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 0.42 (15496 hom., cov: 32)
  • Exomes 𝑓: 0.51 (61 hom.)
• Consequence: GTF2H1 NM_005316.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.00

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.4).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.569 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GTF2H1	NM_005316.4	c.*712G>C		3_prime_UTR_variant	15/15	ENST00000265963.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GTF2H1	ENST00000265963.9	c.*712G>C		3_prime_UTR_variant	15/15	1	NM_005316.4	P1
GTF2H1	ENST00000534641.5	c.*712G>C		3_prime_UTR_variant	14/14	2

Frequencies

GnomAD3 genomes AF: 0.417 AC: 63391 AN: 151920 Hom.: 15496 Cov.: 32

Gnomad AFR AF: 0.150

Gnomad AMI AF: 0.645

Gnomad AMR AF: 0.481

Gnomad ASJ AF: 0.367

Gnomad EAS AF: 0.586

Gnomad SAS AF: 0.404

Gnomad FIN AF: 0.517

Gnomad MID AF: 0.316

Gnomad NFE AF: 0.539

Gnomad OTH AF: 0.403

GnomAD4 exome AF: 0.514 AC: 223 AN: 434 Hom.: 61 Cov.: 0 AF XY: 0.542 AC XY: 142 AN XY: 262

Gnomad4 FIN exome AF: 0.514

Gnomad4 NFE exome AF: 0.500

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.417 AC: 63402 AN: 152038 Hom.: 15496 Cov.: 32 AF XY: 0.418 AC XY: 31017 AN XY: 74282

Gnomad4 AFR AF: 0.150

Gnomad4 AMR AF: 0.481

Gnomad4 ASJ AF: 0.367

Gnomad4 EAS AF: 0.586

Gnomad4 SAS AF: 0.405

Gnomad4 FIN AF: 0.517

Gnomad4 NFE AF: 0.538

Gnomad4 OTH AF: 0.403

Alfa AF: 0.453 Hom.: 2104

Bravo AF: 0.404

Asia WGS AF: 0.456 AC: 1583 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.40
CADD	Benign	17
DANN	Benign	0.88

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs4596; hg19: chr11-18388128;