chr11-18361364-C-T

Variant names:

• chr11-18361364-C-T
• rs4150667
• NM_005316.4:c.1560+657C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005316.4(GTF2H1):​c.1560+657C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.237 in 151,908 control chromosomes in the GnomAD database, including 5,141 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 0.24 (5141 hom., cov: 31)
• Consequence: GTF2H1 NM_005316.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.37
• Publications: 15 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.319 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GTF2H1	NM_005316.4	c.1560+657C>T		intron_variant	Intron 14 of 14	ENST00000265963.9	NP_005307.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GTF2H1	ENST00000265963.9	c.1560+657C>T		intron_variant	Intron 14 of 14	1	NM_005316.4	ENSP00000265963.4

Frequencies

GnomAD3 genomes AF: 0.237 AC: 36004 AN: 151790 Hom.: 5141 Cov.: 31

Gnomad AFR AF: 0.0708

Gnomad AMI AF: 0.439

Gnomad AMR AF: 0.269

Gnomad ASJ AF: 0.288

Gnomad EAS AF: 0.323

Gnomad SAS AF: 0.263

Gnomad FIN AF: 0.206

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.323

Gnomad OTH AF: 0.240

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

GnomAD4 genome AF: 0.237 AC: 35998 AN: 151908 Hom.: 5141 Cov.: 31 AF XY: 0.231 AC XY: 17163 AN XY: 74250

African (AFR) AF: 0.0705 AC: 2928 AN: 41520

American (AMR) AF: 0.269 AC: 4090 AN: 15216

Ashkenazi Jewish (ASJ) AF: 0.288 AC: 998 AN: 3468

East Asian (EAS) AF: 0.324 AC: 1650 AN: 5100

South Asian (SAS) AF: 0.263 AC: 1269 AN: 4816

European-Finnish (FIN) AF: 0.206 AC: 2179 AN: 10556

Middle Eastern (MID) AF: 0.218 AC: 64 AN: 294

European-Non Finnish (NFE) AF: 0.323 AC: 21921 AN: 67920

Other (OTH) AF: 0.237 AC: 500 AN: 2110

Alfa AF: 0.299 Hom.: 12255

Bravo AF: 0.238

Asia WGS AF: 0.290 AC: 1009 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.69
DANN	Benign	0.68
PhyloP100		-1.4
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4150667; hg19: chr11-18382911;