chr11-18344321-G-A

Variant names:

• chr11-18344321-G-A
• rs4150628
• NM_005316.4:c.837+2714G>A

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+2714G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.461 in 151,818 control chromosomes in the GnomAD database, including 18,533 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 0.46 (18533 hom., cov: 31)
• Consequence: GTF2H1 NM_005316.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.718
• 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.825 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GTF2H1	NM_005316.4	c.837+2714G>A		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+2714G>A		intron_variant	Intron 7 of 14	1	NM_005316.4	ENSP00000265963.4

Frequencies

GnomAD3 genomes AF: 0.461 AC: 69955 AN: 151702 Hom.: 18529 Cov.: 31

Gnomad AFR AF: 0.196

Gnomad AMI AF: 0.673

Gnomad AMR AF: 0.524

Gnomad ASJ AF: 0.425

Gnomad EAS AF: 0.846

Gnomad SAS AF: 0.531

Gnomad FIN AF: 0.525

Gnomad MID AF: 0.358

Gnomad NFE AF: 0.564

Gnomad OTH AF: 0.444

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

GnomAD4 genome AF: 0.461 AC: 69980 AN: 151818 Hom.: 18533 Cov.: 31 AF XY: 0.464 AC XY: 34435 AN XY: 74226

African (AFR) AF: 0.196 AC: 8112 AN: 41364

American (AMR) AF: 0.524 AC: 7983 AN: 15236

Ashkenazi Jewish (ASJ) AF: 0.425 AC: 1475 AN: 3468

East Asian (EAS) AF: 0.846 AC: 4369 AN: 5166

South Asian (SAS) AF: 0.533 AC: 2566 AN: 4818

European-Finnish (FIN) AF: 0.525 AC: 5530 AN: 10532

Middle Eastern (MID) AF: 0.361 AC: 106 AN: 294

European-Non Finnish (NFE) AF: 0.564 AC: 38281 AN: 67922

Other (OTH) AF: 0.449 AC: 946 AN: 2108

Alfa AF: 0.480 Hom.: 2504

Bravo AF: 0.453

Asia WGS AF: 0.658 AC: 2283 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.4
DANN	Benign	0.76
PhyloP100		0.72
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: rs4150628; hg19: chr11-18365868;