NM_001517.5:c.560+51C>T

Variant names:

• chr6-30910992-C-T
• rs3218815
• NM_001517.5:c.560+51C>T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001517.5(GTF2H4):​c.560+51C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.226 in 1,464,722 control chromosomes in the GnomAD database, including 46,930 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 0.26 (6017 hom., cov: 31)
  • Exomes 𝑓: 0.22 (40913 hom.)
• Consequence: GTF2H4 NM_001517.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0580

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.59 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GTF2H4	NM_001517.5	c.560+51C>T		intron_variant	Intron 6 of 13	ENST00000259895.9	NP_001508.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GTF2H4	ENST00000259895.9	c.560+51C>T		intron_variant	Intron 6 of 13	1	NM_001517.5	ENSP00000259895.4
GTF2H4	ENST00000376316.5	c.560+51C>T		intron_variant	Intron 6 of 13	5		ENSP00000365493.2
ENSG00000288473	ENST00000477288.5	n.725+51C>T		intron_variant	Intron 6 of 40	2
GTF2H4	ENST00000487746.1	n.416+51C>T		intron_variant	Intron 4 of 7	5

Frequencies

GnomAD3 genomes AF: 0.260 AC: 39409 AN: 151654 Hom.: 6003 Cov.: 31

Gnomad AFR AF: 0.272

Gnomad AMI AF: 0.299

Gnomad AMR AF: 0.367

Gnomad ASJ AF: 0.255

Gnomad EAS AF: 0.607

Gnomad SAS AF: 0.511

Gnomad FIN AF: 0.256

Gnomad MID AF: 0.226

Gnomad NFE AF: 0.185

Gnomad OTH AF: 0.255

GnomAD3 exomes AF: 0.315 AC: 57219 AN: 181890 Hom.: 11046 AF XY: 0.316 AC XY: 31001 AN XY: 98054

Gnomad AFR exome AF: 0.267

Gnomad AMR exome AF: 0.465

Gnomad ASJ exome AF: 0.260

Gnomad EAS exome AF: 0.588

Gnomad SAS exome AF: 0.465

Gnomad FIN exome AF: 0.256

Gnomad NFE exome AF: 0.188

Gnomad OTH exome AF: 0.276

GnomAD4 exome AF: 0.222 AC: 291098 AN: 1312950 Hom.: 40913 Cov.: 19 AF XY: 0.229 AC XY: 149880 AN XY: 655610

Gnomad4 AFR exome AF: 0.257

Gnomad4 AMR exome AF: 0.453

Gnomad4 ASJ exome AF: 0.265

Gnomad4 EAS exome AF: 0.578

Gnomad4 SAS exome AF: 0.469

Gnomad4 FIN exome AF: 0.259

Gnomad4 NFE exome AF: 0.173

Gnomad4 OTH exome AF: 0.262

GnomAD4 genome AF: 0.260 AC: 39446 AN: 151772 Hom.: 6017 Cov.: 31 AF XY: 0.270 AC XY: 20041 AN XY: 74150

Gnomad4 AFR AF: 0.271

Gnomad4 AMR AF: 0.367

Gnomad4 ASJ AF: 0.255

Gnomad4 EAS AF: 0.608

Gnomad4 SAS AF: 0.509

Gnomad4 FIN AF: 0.256

Gnomad4 NFE AF: 0.185

Gnomad4 OTH AF: 0.262

Alfa AF: 0.216 Hom.: 2875

Bravo AF: 0.266

Asia WGS AF: 0.551 AC: 1912 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	5.8
DANN	Benign	0.60

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs3218815; hg19: chr6-30878769;