6-30908375-C-A

Variant names:

• chr6-30908375-C-A
• rs1052693
• NM_001517.5:c.-32C>A

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.-32C>A variant causes a 5 prime UTR 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: 32)
• Consequence: GTF2H4 NM_001517.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.237
• Publications: 33 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=-0.54).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GTF2H4	NM_001517.5	c.-32C>A		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	ENST00000259895.9	c.-32C>A		5_prime_UTR_variant	Exon 1 of 14	1	NM_001517.5	ENSP00000259895.4
GTF2H4	ENST00000453897.4	n.153C>A		non_coding_transcript_exon_variant	Exon 1 of 5	5
ENSG00000288473	ENST00000477288.5	n.134C>A		non_coding_transcript_exon_variant	Exon 1 of 41	2
GTF2H4	ENST00000376316.5	c.-7C>A		5_prime_UTR_variant	Exon 1 of 14	5		ENSP00000365493.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 10084

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	15
DANN	Benign	0.93
PhyloP100		-0.24
PromoterAI		-0.082	Neutral

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs1052693; hg19: chr6-30876152;