chr11-18333555-T-G

Variant names:

• chr11-18333555-T-G
• rs4150563
• NM_005316.4:c.154+327T>G

Variant summary

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

The NM_005316.4(GTF2H1):​c.154+327T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.157 in 174,586 control chromosomes in the GnomAD database, including 2,845 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 0.15 (2326 hom., cov: 33)
  • Exomes 𝑓: 0.19 (519 hom.)
• Consequence: GTF2H1 NM_005316.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.07
• Publications: 7 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=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.211 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GTF2H1	NM_005316.4	c.154+327T>G		intron_variant	Intron 2 of 14	ENST00000265963.9	NP_005307.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GTF2H1	ENST00000265963.9	c.154+327T>G		intron_variant	Intron 2 of 14	1	NM_005316.4	ENSP00000265963.4

Frequencies

GnomAD3 genomes AF: 0.152 AC: 23151 AN: 152126 Hom.: 2324 Cov.: 33

Gnomad AFR AF: 0.0383

Gnomad AMI AF: 0.207

Gnomad AMR AF: 0.142

Gnomad ASJ AF: 0.0748

Gnomad EAS AF: 0.0391

Gnomad SAS AF: 0.115

Gnomad FIN AF: 0.310

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.214

Gnomad OTH AF: 0.140

GnomAD4 exome AF: 0.190 AC: 4237 AN: 22342 Hom.: 519 Cov.: 0 AF XY: 0.185 AC XY: 2116 AN XY: 11416

African (AFR) AF: 0.0270 AC: 19 AN: 704

American (AMR) AF: 0.118 AC: 107 AN: 908

Ashkenazi Jewish (ASJ) AF: 0.0839 AC: 69 AN: 822

East Asian (EAS) AF: 0.0319 AC: 43 AN: 1346

South Asian (SAS) AF: 0.116 AC: 140 AN: 1208

European-Finnish (FIN) AF: 0.324 AC: 249 AN: 768

Middle Eastern (MID) AF: 0.0980 AC: 10 AN: 102

European-Non Finnish (NFE) AF: 0.221 AC: 3332 AN: 15078

Other (OTH) AF: 0.191 AC: 268 AN: 1406

GnomAD4 genome AF: 0.152 AC: 23151 AN: 152244 Hom.: 2326 Cov.: 33 AF XY: 0.156 AC XY: 11621 AN XY: 74432

African (AFR) AF: 0.0382 AC: 1588 AN: 41570

American (AMR) AF: 0.142 AC: 2168 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0748 AC: 259 AN: 3464

East Asian (EAS) AF: 0.0391 AC: 203 AN: 5186

South Asian (SAS) AF: 0.116 AC: 559 AN: 4832

European-Finnish (FIN) AF: 0.310 AC: 3281 AN: 10576

Middle Eastern (MID) AF: 0.105 AC: 31 AN: 294

European-Non Finnish (NFE) AF: 0.214 AC: 14579 AN: 67998

Other (OTH) AF: 0.139 AC: 294 AN: 2114

Alfa AF: 0.179 Hom.: 5664

Bravo AF: 0.133

Asia WGS AF: 0.0740 AC: 255 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	7.6
DANN	Benign	0.72
PhyloP100		1.1
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: rs4150563; hg19: chr11-18355102;