NM_005316.4:c.1260+1540G>A

Variant names:

• chr11-18353986-G-A
• rs7103375
• NM_005316.4:c.1260+1540G>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.1260+1540G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.865 in 152,276 control chromosomes in the GnomAD database, including 57,337 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 0.87 (57337 hom., cov: 33)
• Consequence: GTF2H1 NM_005316.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0760
• Publications: 11 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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.946 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GTF2H1	NM_005316.4	MANE Select	c.1260+1540G>A		intron	N/A	NP_005307.1
	GTF2H1	NM_001142307.2		c.1260+1540G>A		intron	N/A	NP_001135779.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GTF2H1	ENST00000265963.9	TSL:1 MANE Select	c.1260+1540G>A		intron	N/A	ENSP00000265963.4
	GTF2H1	ENST00000453096.6	TSL:2	c.1260+1540G>A		intron	N/A	ENSP00000393638.2
	GTF2H1	ENST00000534641.5	TSL:2	c.912+1540G>A		intron	N/A	ENSP00000435375.1

Frequencies

GnomAD3 genomes AF: 0.865 AC: 131616 AN: 152158 Hom.: 57282 Cov.: 33

Gnomad AFR AF: 0.950

Gnomad AMI AF: 0.818

Gnomad AMR AF: 0.835

Gnomad ASJ AF: 0.725

Gnomad EAS AF: 0.968

Gnomad SAS AF: 0.793

Gnomad FIN AF: 0.867

Gnomad MID AF: 0.703

Gnomad NFE AF: 0.826

Gnomad OTH AF: 0.830

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

GnomAD4 genome AF: 0.865 AC: 131732 AN: 152276 Hom.: 57337 Cov.: 33 AF XY: 0.865 AC XY: 64358 AN XY: 74440

African (AFR) AF: 0.950 AC: 39494 AN: 41574

American (AMR) AF: 0.835 AC: 12757 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.725 AC: 2518 AN: 3472

East Asian (EAS) AF: 0.968 AC: 5026 AN: 5192

South Asian (SAS) AF: 0.793 AC: 3829 AN: 4826

European-Finnish (FIN) AF: 0.867 AC: 9197 AN: 10602

Middle Eastern (MID) AF: 0.694 AC: 204 AN: 294

European-Non Finnish (NFE) AF: 0.826 AC: 56204 AN: 68010

Other (OTH) AF: 0.832 AC: 1757 AN: 2112

Alfa AF: 0.828 Hom.: 43696

Bravo AF: 0.868

Asia WGS AF: 0.916 AC: 3180 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.33
DANN	Benign	0.54
PhyloP100		-0.076
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: rs7103375; hg19: chr11-18375533;