6-30908257-G-T

Variant names:

• chr6-30908257-G-T
• rs2074510
• NM_001517.5:c.-150G>T

Variant summary

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

The NM_001517.5(GTF2H4):​c.-150G>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 153,302 control chromosomes in the GnomAD database, including 6,064 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 (6046 hom., cov: 32)
  • Exomes 𝑓: 0.14 (18 hom.)
• Consequence: GTF2H4 NM_001517.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.674

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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.591 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GTF2H4	NM_001517.5	c.-150G>T		5_prime_UTR_variant	Exon 1 of 14	ENST00000259895.9	NP_001508.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GTF2H4	ENST00000259895	c.-150G>T		5_prime_UTR_variant	Exon 1 of 14	1	NM_001517.5	ENSP00000259895.4
GTF2H4	ENST00000376316	c.-125G>T		5_prime_UTR_variant	Exon 1 of 14	5		ENSP00000365493.2
GTF2H4	ENST00000453897.4	n.35G>T		non_coding_transcript_exon_variant	Exon 1 of 5	5
ENSG00000288473	ENST00000477288.5	n.16G>T		non_coding_transcript_exon_variant	Exon 1 of 41	2

Frequencies

GnomAD3 genomes AF: 0.260 AC: 39513 AN: 151942 Hom.: 6032 Cov.: 32

Gnomad AFR AF: 0.271

Gnomad AMI AF: 0.299

Gnomad AMR AF: 0.367

Gnomad ASJ AF: 0.256

Gnomad EAS AF: 0.608

Gnomad SAS AF: 0.510

Gnomad FIN AF: 0.257

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.185

Gnomad OTH AF: 0.255

GnomAD4 exome AF: 0.140 AC: 174 AN: 1242 Hom.: 18 Cov.: 0 AF XY: 0.136 AC XY: 85 AN XY: 624

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.244

Gnomad4 ASJ exome AF: 0.250

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 0.289

Gnomad4 FIN exome AF: 0.111

Gnomad4 NFE exome AF: 0.0996

Gnomad4 OTH exome AF: 0.205

GnomAD4 genome AF: 0.260 AC: 39550 AN: 152060 Hom.: 6046 Cov.: 32 AF XY: 0.271 AC XY: 20114 AN XY: 74334

Gnomad4 AFR AF: 0.271

Gnomad4 AMR AF: 0.368

Gnomad4 ASJ AF: 0.256

Gnomad4 EAS AF: 0.609

Gnomad4 SAS AF: 0.509

Gnomad4 FIN AF: 0.257

Gnomad4 NFE AF: 0.186

Gnomad4 OTH AF: 0.262

Alfa AF: 0.190 Hom.: 1953

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	-0.92
CADD	Benign	12
DANN	Benign	0.69
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Publications

LitVar

Other links and lift over

dbSNP: rs2074510; hg19: chr6-30876034;