rs4237721

Variant names:

• chr11-18348800-C-T
• rs4237721
• NM_005316.4:c.1053+881C>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.1053+881C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.139 in 152,092 control chromosomes in the GnomAD database, including 1,567 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 0.14 (1567 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: GTF2H1 NM_005316.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.573
• Publications: 6 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 (AFR) allele frequency at 95% confidence interval = 0.184 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GTF2H1	NM_005316.4	c.1053+881C>T		intron_variant	Intron 9 of 14	ENST00000265963.9	NP_005307.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GTF2H1	ENST00000265963.9	c.1053+881C>T		intron_variant	Intron 9 of 14	1	NM_005316.4	ENSP00000265963.4

Frequencies

GnomAD3 genomes AF: 0.139 AC: 21055 AN: 151974 Hom.: 1564 Cov.: 32

Gnomad AFR AF: 0.187

Gnomad AMI AF: 0.0549

Gnomad AMR AF: 0.155

Gnomad ASJ AF: 0.123

Gnomad EAS AF: 0.119

Gnomad SAS AF: 0.130

Gnomad FIN AF: 0.176

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.103

Gnomad OTH AF: 0.150

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.139 AC: 21067 AN: 152092 Hom.: 1567 Cov.: 32 AF XY: 0.141 AC XY: 10512 AN XY: 74316

African (AFR) AF: 0.187 AC: 7765 AN: 41472

American (AMR) AF: 0.155 AC: 2373 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.123 AC: 428 AN: 3470

East Asian (EAS) AF: 0.119 AC: 616 AN: 5186

South Asian (SAS) AF: 0.129 AC: 622 AN: 4820

European-Finnish (FIN) AF: 0.176 AC: 1860 AN: 10556

Middle Eastern (MID) AF: 0.139 AC: 41 AN: 294

European-Non Finnish (NFE) AF: 0.103 AC: 6999 AN: 68002

Other (OTH) AF: 0.149 AC: 313 AN: 2106

Alfa AF: 0.136 Hom.: 274

Bravo AF: 0.139

Asia WGS AF: 0.141 AC: 490 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	2.0
DANN	Benign	0.59
PhyloP100		-0.57
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: rs4237721; hg19: chr11-18370347;