rs4150581

Positions:

• chr11-18335723-A-G

Variant summary

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

The NM_005316.4(GTF2H1):​c.155-31A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.522 in 1,524,534 control chromosomes in the GnomAD database, including 216,994 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. There are indicators that this mutation may affect the branch point..

• Frequency:
  • Genomes: 𝑓 0.42 (15570 hom., cov: 33)
  • Exomes 𝑓: 0.53 (201424 hom.)
• Consequence: GTF2H1 NM_005316.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.170

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: This place is a probable branch point but likely benign (scored 1 / 10). Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.57 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GTF2H1	NM_005316.4	c.155-31A>G		intron_variant		ENST00000265963.9	NP_005307.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GTF2H1	ENST00000265963.9	c.155-31A>G		intron_variant		1	NM_005316.4	ENSP00000265963.4

Frequencies

GnomAD3 genomes AF: 0.418 AC: 63521 AN: 152030 Hom.: 15570 Cov.: 33

Gnomad AFR AF: 0.150

Gnomad AMI AF: 0.646

Gnomad AMR AF: 0.482

Gnomad ASJ AF: 0.367

Gnomad EAS AF: 0.587

Gnomad SAS AF: 0.403

Gnomad FIN AF: 0.517

Gnomad MID AF: 0.315

Gnomad NFE AF: 0.540

Gnomad OTH AF: 0.406

GnomAD3 exomes AF: 0.477 AC: 115961 AN: 242932 Hom.: 29202 AF XY: 0.478 AC XY: 62742 AN XY: 131334

Gnomad AFR exome AF: 0.142

Gnomad AMR exome AF: 0.502

Gnomad ASJ exome AF: 0.372

Gnomad EAS exome AF: 0.573

Gnomad SAS exome AF: 0.390

Gnomad FIN exome AF: 0.525

Gnomad NFE exome AF: 0.527

Gnomad OTH exome AF: 0.465

GnomAD4 exome AF: 0.533 AC: 731530 AN: 1372384 Hom.: 201424 Cov.: 20 AF XY: 0.528 AC XY: 362459 AN XY: 686998

Gnomad4 AFR exome AF: 0.129

Gnomad4 AMR exome AF: 0.500

Gnomad4 ASJ exome AF: 0.372

Gnomad4 EAS exome AF: 0.566

Gnomad4 SAS exome AF: 0.386

Gnomad4 FIN exome AF: 0.526

Gnomad4 NFE exome AF: 0.565

Gnomad4 OTH exome AF: 0.496

GnomAD4 genome AF: 0.418 AC: 63533 AN: 152150 Hom.: 15570 Cov.: 33 AF XY: 0.418 AC XY: 31080 AN XY: 74356

Gnomad4 AFR AF: 0.150

Gnomad4 AMR AF: 0.482

Gnomad4 ASJ AF: 0.367

Gnomad4 EAS AF: 0.587

Gnomad4 SAS AF: 0.404

Gnomad4 FIN AF: 0.517

Gnomad4 NFE AF: 0.539

Gnomad4 OTH AF: 0.405

Alfa AF: 0.480 Hom.: 10109

Bravo AF: 0.405

Asia WGS AF: 0.456 AC: 1584 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	9.0
DANN	Benign	0.64
BranchPoint Hunter		1.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs4150581; hg19: chr11-18357270;