6-30908257-G-T

Variant names:

• chr6-30908257-G-T
• rs2074510
• NM_001517.5:c.-150G>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.-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
• Publications: 24 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.591 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001517.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GTF2H4	NM_001517.5	MANE Select	c.-150G>T		5_prime_UTR	Exon 1 of 14	NP_001508.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GTF2H4	ENST00000259895.9	TSL:1 MANE Select	c.-150G>T		5_prime_UTR	Exon 1 of 14	ENSP00000259895.4
	GTF2H4	ENST00000453897.4	TSL:5	n.35G>T		non_coding_transcript_exon	Exon 1 of 5
	ENSG00000288473	ENST00000477288.5	TSL:2	n.16G>T		non_coding_transcript_exon	Exon 1 of 41

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

African (AFR) AF: 0.00 AC: 0 AN: 2

American (AMR) AF: 0.244 AC: 38 AN: 156

Ashkenazi Jewish (ASJ) AF: 0.250 AC: 1 AN: 4

East Asian (EAS) AF: 1.00 AC: 2 AN: 2

South Asian (SAS) AF: 0.289 AC: 22 AN: 76

European-Finnish (FIN) AF: 0.111 AC: 2 AN: 18

Middle Eastern (MID) AF: 0.346 AC: 9 AN: 26

European-Non Finnish (NFE) AF: 0.0996 AC: 91 AN: 914

Other (OTH) AF: 0.205 AC: 9 AN: 44

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

African (AFR) AF: 0.271 AC: 11220 AN: 41418

American (AMR) AF: 0.368 AC: 5620 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.256 AC: 888 AN: 3472

East Asian (EAS) AF: 0.609 AC: 3151 AN: 5178

South Asian (SAS) AF: 0.509 AC: 2453 AN: 4818

European-Finnish (FIN) AF: 0.257 AC: 2711 AN: 10566

Middle Eastern (MID) AF: 0.224 AC: 66 AN: 294

European-Non Finnish (NFE) AF: 0.186 AC: 12616 AN: 68006

Other (OTH) AF: 0.262 AC: 552 AN: 2108

Alfa AF: 0.220 Hom.: 6252

Bravo AF: 0.266

Asia WGS AF: 0.551 AC: 1913 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	12
DANN	Benign	0.69
PhyloP100		0.67
PromoterAI		0.052	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=300/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2074510; hg19: chr6-30876034;