6-30912210-C-T

Variant names:

• chr6-30912210-C-T
• rs1264308
• NM_001517.5:c.958+64C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001517.5(GTF2H4):​c.958+64C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.115 in 1,603,026 control chromosomes in the GnomAD database, including 12,997 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 0.075 (609 hom., cov: 31)
  • Exomes 𝑓: 0.12 (12388 hom.)
• Consequence: GTF2H4 NM_001517.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0660
• Publications: 33 publications found

Genes affected

GTF2H4 (HGNC:4658): (general transcription factor IIH subunit 4) Enables RNA polymerase II general transcription initiation factor activity. Involved in transcription by RNA polymerase II. Located in nuclear speck. Part of core TFIIH complex portion of holo TFIIH complex and transcription factor TFIID complex. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000288473 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.117 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GTF2H4	NM_001517.5	c.958+64C>T		intron_variant	Intron 10 of 13	ENST00000259895.9	NP_001508.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GTF2H4	ENST00000259895.9	c.958+64C>T		intron_variant	Intron 10 of 13	1	NM_001517.5	ENSP00000259895.4

Frequencies

GnomAD3 genomes AF: 0.0745 AC: 11326 AN: 151968 Hom.: 609 Cov.: 31

Gnomad AFR AF: 0.0326

Gnomad AMI AF: 0.146

Gnomad AMR AF: 0.0294

Gnomad ASJ AF: 0.0444

Gnomad EAS AF: 0.00405

Gnomad SAS AF: 0.0536

Gnomad FIN AF: 0.0703

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.119

Gnomad OTH AF: 0.0533

GnomAD4 exome AF: 0.119 AC: 173109 AN: 1450940 Hom.: 12388 Cov.: 32 AF XY: 0.118 AC XY: 85044 AN XY: 721056

African (AFR) AF: 0.0328 AC: 1091 AN: 33292

American (AMR) AF: 0.0224 AC: 993 AN: 44384

Ashkenazi Jewish (ASJ) AF: 0.0441 AC: 1127 AN: 25584

East Asian (EAS) AF: 0.00104 AC: 41 AN: 39606

South Asian (SAS) AF: 0.0695 AC: 5926 AN: 85240

European-Finnish (FIN) AF: 0.0746 AC: 3859 AN: 51730

Middle Eastern (MID) AF: 0.0390 AC: 223 AN: 5722

European-Non Finnish (NFE) AF: 0.139 AC: 153709 AN: 1105346

Other (OTH) AF: 0.102 AC: 6140 AN: 60036

GnomAD4 genome AF: 0.0746 AC: 11351 AN: 152086 Hom.: 609 Cov.: 31 AF XY: 0.0695 AC XY: 5167 AN XY: 74328

African (AFR) AF: 0.0331 AC: 1374 AN: 41488

American (AMR) AF: 0.0293 AC: 448 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0444 AC: 154 AN: 3468

East Asian (EAS) AF: 0.00406 AC: 21 AN: 5178

South Asian (SAS) AF: 0.0547 AC: 263 AN: 4810

European-Finnish (FIN) AF: 0.0703 AC: 745 AN: 10596

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.119 AC: 8098 AN: 67948

Other (OTH) AF: 0.0527 AC: 111 AN: 2106

Alfa AF: 0.106 Hom.: 4047

Bravo AF: 0.0694

Asia WGS AF: 0.0210 AC: 73 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	6.2
DANN	Benign	0.54
PhyloP100		-0.066
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs1264308; hg19: chr6-30879987;