6-30908461-G-T

Variant names:

• chr6-30908461-G-T
• rs2074509
• NM_001517.5:c.-4+58G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001517.5(GTF2H4):​c.-4+58G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: GTF2H4 NM_001517.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.288
• Publications: 4 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).

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.-4+58G>T		intron	N/A	NP_001508.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GTF2H4	ENST00000259895.9	TSL:1 MANE Select	c.-4+58G>T		intron	N/A	ENSP00000259895.4
	GTF2H4	ENST00000376316.5	TSL:5	c.-4+83G>T		intron	N/A	ENSP00000365493.2
	GTF2H4	ENST00000453897.4	TSL:5	n.181+58G>T		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 15744 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 8476

African (AFR) AF: 0.00 AC: 0 AN: 140

American (AMR) AF: 0.00 AC: 0 AN: 2642

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 128

East Asian (EAS) AF: 0.00 AC: 0 AN: 194

South Asian (SAS) AF: 0.00 AC: 0 AN: 2320

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 248

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1662

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 7670

Other (OTH) AF: 0.00 AC: 0 AN: 740

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	6.1
DANN	Benign	0.66
PhyloP100		0.29
PromoterAI		-0.021	Neutral

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs2074509; hg19: chr6-30876238;