6-30908375-C-T

Position:

• chr6-30908375-C-T

Variant summary

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

The NM_001517.5(GTF2H4):​c.-32C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.259 in 154,266 control chromosomes in the GnomAD database, including 6,097 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 (6021 hom., cov: 32)
  • Exomes 𝑓: 0.22 (76 hom.)
• Consequence: GTF2H4 NM_001517.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.237

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.56).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.589 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GTF2H4	NM_001517.5	c.-32C>T		5_prime_UTR_variant	1/14	ENST00000259895.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GTF2H4	ENST00000259895.9	c.-32C>T		5_prime_UTR_variant	1/14	1	NM_001517.5	P1
GTF2H4	ENST00000376316.5	c.-7C>T		5_prime_UTR_variant	1/14	5		P1
GTF2H4	ENST00000453897.4	n.153C>T		non_coding_transcript_exon_variant	1/5	5

Frequencies

GnomAD3 genomes AF: 0.260 AC: 39369 AN: 151698 Hom.: 6007 Cov.: 32

Gnomad AFR AF: 0.271

Gnomad AMI AF: 0.297

Gnomad AMR AF: 0.367

Gnomad ASJ AF: 0.255

Gnomad EAS AF: 0.606

Gnomad SAS AF: 0.509

Gnomad FIN AF: 0.255

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.185

Gnomad OTH AF: 0.255

GnomAD4 exome AF: 0.223 AC: 547 AN: 2450 Hom.: 76 Cov.: 0 AF XY: 0.228 AC XY: 287 AN XY: 1258

Gnomad4 AFR exome AF: 0.210

Gnomad4 AMR exome AF: 0.328

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.438

Gnomad4 FIN exome AF: 0.429

Gnomad4 NFE exome AF: 0.104

Gnomad4 OTH exome AF: 0.330

GnomAD4 genome AF: 0.260 AC: 39406 AN: 151816 Hom.: 6021 Cov.: 32 AF XY: 0.270 AC XY: 20013 AN XY: 74174

Gnomad4 AFR AF: 0.271

Gnomad4 AMR AF: 0.367

Gnomad4 ASJ AF: 0.255

Gnomad4 EAS AF: 0.607

Gnomad4 SAS AF: 0.508

Gnomad4 FIN AF: 0.255

Gnomad4 NFE AF: 0.185

Gnomad4 OTH AF: 0.263

Alfa AF: 0.190 Hom.: 2140

Bravo AF: 0.266

Asia WGS AF: 0.551 AC: 1913 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	16
DANN	Benign	0.94

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs1052693; hg19: chr6-30876152;