11-18353617-A-T

Variant names:

• chr11-18353617-A-T
• rs4150655
• NM_005316.4:c.1260+1171A>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.1260+1171A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.677 in 152,154 control chromosomes in the GnomAD database, including 35,378 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 0.68 (35378 hom., cov: 34)
• Consequence: GTF2H1 NM_005316.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0920
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.941 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005316.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GTF2H1	NM_005316.4	MANE Select	c.1260+1171A>T		intron	N/A	NP_005307.1	P32780-1
	GTF2H1	NM_001142307.2		c.1260+1171A>T		intron	N/A	NP_001135779.1	P32780-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GTF2H1	ENST00000265963.9	TSL:1 MANE Select	c.1260+1171A>T		intron	N/A	ENSP00000265963.4	P32780-1
	GTF2H1	ENST00000928992.1		c.1293+1171A>T		intron	N/A	ENSP00000599051.1
	GTF2H1	ENST00000453096.6	TSL:2	c.1260+1171A>T		intron	N/A	ENSP00000393638.2	P32780-1

Frequencies

GnomAD3 genomes AF: 0.677 AC: 102951 AN: 152036 Hom.: 35367 Cov.: 34

Gnomad AFR AF: 0.604

Gnomad AMI AF: 0.762

Gnomad AMR AF: 0.728

Gnomad ASJ AF: 0.592

Gnomad EAS AF: 0.964

Gnomad SAS AF: 0.665

Gnomad FIN AF: 0.719

Gnomad MID AF: 0.585

Gnomad NFE AF: 0.687

Gnomad OTH AF: 0.666

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

GnomAD4 genome AF: 0.677 AC: 103010 AN: 152154 Hom.: 35378 Cov.: 34 AF XY: 0.681 AC XY: 50638 AN XY: 74372

African (AFR) AF: 0.603 AC: 25045 AN: 41502

American (AMR) AF: 0.728 AC: 11134 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.592 AC: 2053 AN: 3470

East Asian (EAS) AF: 0.964 AC: 5000 AN: 5188

South Asian (SAS) AF: 0.666 AC: 3213 AN: 4824

European-Finnish (FIN) AF: 0.719 AC: 7601 AN: 10568

Middle Eastern (MID) AF: 0.575 AC: 169 AN: 294

European-Non Finnish (NFE) AF: 0.687 AC: 46695 AN: 68000

Other (OTH) AF: 0.668 AC: 1407 AN: 2106

Alfa AF: 0.669 Hom.: 4277

Bravo AF: 0.679

Asia WGS AF: 0.813 AC: 2824 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.3
DANN	Benign	0.85
PhyloP100		0.092
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: rs4150655; hg19: chr11-18375164;