11-18362623-C-G

Position:

• chr11-18362623-C-G

Variant summary

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

The NM_005316.4(GTF2H1):​c.1560+1916C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.418 in 148,974 control chromosomes in the GnomAD database, including 15,282 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 (15282 hom., cov: 28)
• Consequence: GTF2H1 NM_005316.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.01

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=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.572 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GTF2H1	NM_005316.4	c.1560+1916C>G		intron_variant		ENST00000265963.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GTF2H1	ENST00000265963.9	c.1560+1916C>G		intron_variant		1	NM_005316.4	P1

Frequencies

GnomAD3 genomes AF: 0.418 AC: 62293 AN: 148892 Hom.: 15283 Cov.: 28

Gnomad AFR AF: 0.150

Gnomad AMI AF: 0.646

Gnomad AMR AF: 0.484

Gnomad ASJ AF: 0.368

Gnomad EAS AF: 0.590

Gnomad SAS AF: 0.404

Gnomad FIN AF: 0.517

Gnomad MID AF: 0.319

Gnomad NFE AF: 0.539

Gnomad OTH AF: 0.404

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

GnomAD4 genome AF: 0.418 AC: 62300 AN: 148974 Hom.: 15282 Cov.: 28 AF XY: 0.418 AC XY: 30337 AN XY: 72492

Gnomad4 AFR AF: 0.150

Gnomad4 AMR AF: 0.484

Gnomad4 ASJ AF: 0.368

Gnomad4 EAS AF: 0.590

Gnomad4 SAS AF: 0.406

Gnomad4 FIN AF: 0.517

Gnomad4 NFE AF: 0.539

Gnomad4 OTH AF: 0.404

Alfa AF: 0.453 Hom.: 2109

Bravo AF: 0.404

Asia WGS AF: 0.454 AC: 1568 AN: 3458

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.26
DANN	Benign	0.31

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: rs4150678; hg19: chr11-18384170;