rs2074509

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr6-30908461-G-A
• chr6-30908461-G-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.-4+58G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.258 in 167,578 control chromosomes in the GnomAD database, including 6,689 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 (6011 hom., cov: 31)
  • Exomes 𝑓: 0.24 (678 hom.)
• 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.59 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GTF2H4	NM_001517.5	c.-4+58G>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+58G>A		intron_variant	Intron 1 of 13	1	NM_001517.5	ENSP00000259895.4
GTF2H4	ENST00000376316.5	c.-4+83G>A		intron_variant	Intron 1 of 13	5		ENSP00000365493.2
GTF2H4	ENST00000453897.4	n.181+58G>A		intron_variant	Intron 1 of 4	5
ENSG00000288473	ENST00000477288.5	n.162+58G>A		intron_variant	Intron 1 of 40	2

Frequencies

GnomAD3 genomes AF: 0.259 AC: 39373 AN: 151734 Hom.: 5997 Cov.: 31

Gnomad AFR AF: 0.271

Gnomad AMI AF: 0.299

Gnomad AMR AF: 0.367

Gnomad ASJ AF: 0.255

Gnomad EAS AF: 0.607

Gnomad SAS AF: 0.510

Gnomad FIN AF: 0.255

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.185

Gnomad OTH AF: 0.255

GnomAD4 exome AF: 0.240 AC: 3770 AN: 15724 Hom.: 678 AF XY: 0.255 AC XY: 2156 AN XY: 8468

African (AFR) AF: 0.179 AC: 25 AN: 140

American (AMR) AF: 0.410 AC: 1078 AN: 2632

Ashkenazi Jewish (ASJ) AF: 0.198 AC: 25 AN: 126

East Asian (EAS) AF: 0.454 AC: 88 AN: 194

South Asian (SAS) AF: 0.403 AC: 934 AN: 2320

European-Finnish (FIN) AF: 0.161 AC: 40 AN: 248

Middle Eastern (MID) AF: 0.218 AC: 362 AN: 1662

European-Non Finnish (NFE) AF: 0.134 AC: 1030 AN: 7662

Other (OTH) AF: 0.254 AC: 188 AN: 740

GnomAD4 genome AF: 0.260 AC: 39410 AN: 151854 Hom.: 6011 Cov.: 31 AF XY: 0.270 AC XY: 20019 AN XY: 74212

African (AFR) AF: 0.270 AC: 11182 AN: 41374

American (AMR) AF: 0.368 AC: 5609 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.255 AC: 884 AN: 3462

East Asian (EAS) AF: 0.608 AC: 3124 AN: 5142

South Asian (SAS) AF: 0.508 AC: 2431 AN: 4782

European-Finnish (FIN) AF: 0.255 AC: 2687 AN: 10552

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

European-Non Finnish (NFE) AF: 0.185 AC: 12600 AN: 67974

Other (OTH) AF: 0.263 AC: 554 AN: 2110

Alfa AF: 0.206 Hom.: 1407

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	-0.86
CADD	Benign	6.6
DANN	Benign	0.71
PhyloP100		0.29
PromoterAI		-0.057	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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;