6-30910992-C-T

Variant names:

• chr6-30910992-C-T
• rs3218815
• NM_001517.5:c.560+51C>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.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
• Publications: 17 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=-0.82).
• 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

GnomAD2 exomes AF: 0.315 AC: 57219 AN: 181890 AF XY: 0.316

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 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

African (AFR) AF: 0.257 AC: 7891 AN: 30690

American (AMR) AF: 0.453 AC: 16884 AN: 37236

Ashkenazi Jewish (ASJ) AF: 0.265 AC: 6525 AN: 24650

East Asian (EAS) AF: 0.578 AC: 21547 AN: 37280

South Asian (SAS) AF: 0.469 AC: 37614 AN: 80184

European-Finnish (FIN) AF: 0.259 AC: 12048 AN: 46584

Middle Eastern (MID) AF: 0.275 AC: 1499 AN: 5442

European-Non Finnish (NFE) AF: 0.173 AC: 172627 AN: 995610

Other (OTH) AF: 0.262 AC: 14463 AN: 55274

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

African (AFR) AF: 0.271 AC: 11215 AN: 41352

American (AMR) AF: 0.367 AC: 5597 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.255 AC: 885 AN: 3466

East Asian (EAS) AF: 0.608 AC: 3121 AN: 5134

South Asian (SAS) AF: 0.509 AC: 2449 AN: 4808

European-Finnish (FIN) AF: 0.256 AC: 2690 AN: 10504

Middle Eastern (MID) AF: 0.226 AC: 66 AN: 292

European-Non Finnish (NFE) AF: 0.185 AC: 12596 AN: 67944

Other (OTH) AF: 0.262 AC: 554 AN: 2114

Alfa AF: 0.228 Hom.: 5400

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
PhyloP100		-0.058
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3218815; hg19: chr6-30878769;