NM_005316.4:c.837+986A>G

Variant names:

• chr11-18342593-A-G
• rs4150610
• NM_005316.4:c.837+986A>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.837+986A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.726 in 152,008 control chromosomes in the GnomAD database, including 40,492 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 0.73 (40492 hom., cov: 31)
• Consequence: GTF2H1 NM_005316.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.22
• Publications: 8 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=-1.08).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.945 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GTF2H1	NM_005316.4	c.837+986A>G		intron_variant	Intron 7 of 14	ENST00000265963.9	NP_005307.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GTF2H1	ENST00000265963.9	c.837+986A>G		intron_variant	Intron 7 of 14	1	NM_005316.4	ENSP00000265963.4

Frequencies

GnomAD3 genomes AF: 0.726 AC: 110259 AN: 151890 Hom.: 40443 Cov.: 31

Gnomad AFR AF: 0.761

Gnomad AMI AF: 0.759

Gnomad AMR AF: 0.746

Gnomad ASJ AF: 0.596

Gnomad EAS AF: 0.967

Gnomad SAS AF: 0.750

Gnomad FIN AF: 0.719

Gnomad MID AF: 0.601

Gnomad NFE AF: 0.688

Gnomad OTH AF: 0.710

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

GnomAD4 genome AF: 0.726 AC: 110364 AN: 152008 Hom.: 40492 Cov.: 31 AF XY: 0.729 AC XY: 54179 AN XY: 74284

African (AFR) AF: 0.762 AC: 31583 AN: 41464

American (AMR) AF: 0.746 AC: 11397 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.596 AC: 2070 AN: 3472

East Asian (EAS) AF: 0.967 AC: 5008 AN: 5178

South Asian (SAS) AF: 0.750 AC: 3604 AN: 4808

European-Finnish (FIN) AF: 0.719 AC: 7582 AN: 10548

Middle Eastern (MID) AF: 0.588 AC: 173 AN: 294

European-Non Finnish (NFE) AF: 0.688 AC: 46750 AN: 67946

Other (OTH) AF: 0.713 AC: 1506 AN: 2112

Alfa AF: 0.696 Hom.: 46796

Bravo AF: 0.732

Asia WGS AF: 0.888 AC: 3085 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.33
DANN	Benign	0.22
PhyloP100		-2.2
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: rs4150610; hg19: chr11-18364140;