rs2074508

Variant names:

• chr6-30908661-G-A
• rs2074508
• NM_001517.5:c.-4+258G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001517.5(GTF2H4):​c.-4+258G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.26 in 152,064 control chromosomes in the GnomAD database, including 6,052 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 (6052 hom., cov: 32)
• Consequence: GTF2H4 NM_001517.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00
• Publications: 13 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=-0.74).
• 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.-4+258G>A		intron_variant	Intron 1 of 13	ENST00000259895.9	NP_001508.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GTF2H4	ENST00000259895.9	c.-4+258G>A		intron_variant	Intron 1 of 13	1	NM_001517.5	ENSP00000259895.4
GTF2H4	ENST00000376316.5	c.-4+283G>A		intron_variant	Intron 1 of 13	5		ENSP00000365493.2
GTF2H4	ENST00000453897.4	n.181+258G>A		intron_variant	Intron 1 of 4	5
ENSG00000288473	ENST00000477288.5	n.162+258G>A		intron_variant	Intron 1 of 40	2

Frequencies

GnomAD3 genomes AF: 0.260 AC: 39519 AN: 151946 Hom.: 6038 Cov.: 32

Gnomad AFR AF: 0.271

Gnomad AMI AF: 0.299

Gnomad AMR AF: 0.368

Gnomad ASJ AF: 0.256

Gnomad EAS AF: 0.608

Gnomad SAS AF: 0.511

Gnomad FIN AF: 0.256

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.185

Gnomad OTH AF: 0.255

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.260 AC: 39556 AN: 152064 Hom.: 6052 Cov.: 32 AF XY: 0.271 AC XY: 20109 AN XY: 74332

African (AFR) AF: 0.271 AC: 11239 AN: 41452

American (AMR) AF: 0.368 AC: 5622 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.256 AC: 888 AN: 3470

East Asian (EAS) AF: 0.608 AC: 3148 AN: 5174

South Asian (SAS) AF: 0.509 AC: 2453 AN: 4816

European-Finnish (FIN) AF: 0.256 AC: 2710 AN: 10580

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

European-Non Finnish (NFE) AF: 0.185 AC: 12605 AN: 67978

Other (OTH) AF: 0.262 AC: 553 AN: 2112

Alfa AF: 0.232 Hom.: 2340

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	-0.74
CADD	Benign	8.6
DANN	Benign	0.88
PhyloP100		0.0
PromoterAI		-0.029	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	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: rs2074508; hg19: chr6-30876438; COSMIC: COSV52558171; COSMIC: COSV52558171;