rs2340693

Positions:

• chr12-123650441-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001516.5(GTF2H3):​c.365-553A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.119 in 153,418 control chromosomes in the GnomAD database, including 2,850 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 0.12 (2850 hom., cov: 32)
  • Exomes 𝑓: 0.018 (0 hom.)
• Consequence: GTF2H3 NM_001516.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.379

Genes affected

GTF2H3 (HGNC:4657): (general transcription factor IIH subunit 3) This gene encodes a member of the TFB4 family. The encoded protein is a subunit of the core-TFIIH basal transcription factor and localizes to the nucleus. The encoded protein is involved in RNA transcription by RNA polymerase II and nucleotide excision repair and associates with the Cdk-activating kinase complex. Alternative splicing results in multiple transcript variants. A related pseudogene has been identified on chromosome 14. [provided by RefSeq, Dec 2012]

ENSG00000279953 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.358 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GTF2H3	NM_001516.5	c.365-553A>G		intron_variant		ENST00000543341.7	NP_001507.2
GTF2H3	NM_001271867.2	c.242-553A>G		intron_variant			NP_001258796.1
GTF2H3	NM_001271866.2	c.365-553A>G		intron_variant			NP_001258795.1
GTF2H3	NM_001271868.2	c.-74-553A>G		intron_variant			NP_001258797.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GTF2H3	ENST00000543341.7	c.365-553A>G		intron_variant		1	NM_001516.5	ENSP00000445162.1

Frequencies

GnomAD3 genomes AF: 0.120 AC: 18210 AN: 152056 Hom.: 2843 Cov.: 32

Gnomad AFR AF: 0.363

Gnomad AMI AF: 0.0570

Gnomad AMR AF: 0.0560

Gnomad ASJ AF: 0.0514

Gnomad EAS AF: 0.00327

Gnomad SAS AF: 0.0515

Gnomad FIN AF: 0.00706

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0231

Gnomad OTH AF: 0.0959

GnomAD4 exome AF: 0.0185 AC: 23 AN: 1244 Hom.: 0 Cov.: 0 AF XY: 0.0222 AC XY: 15 AN XY: 676

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0211

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0233

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0195

Gnomad4 OTH exome AF: 0.0185

GnomAD4 genome AF: 0.120 AC: 18265 AN: 152174 Hom.: 2850 Cov.: 32 AF XY: 0.116 AC XY: 8635 AN XY: 74416

Gnomad4 AFR AF: 0.363

Gnomad4 AMR AF: 0.0559

Gnomad4 ASJ AF: 0.0514

Gnomad4 EAS AF: 0.00347

Gnomad4 SAS AF: 0.0519

Gnomad4 FIN AF: 0.00706

Gnomad4 NFE AF: 0.0231

Gnomad4 OTH AF: 0.0944

Alfa AF: 0.0844 Hom.: 642

Bravo AF: 0.135

Asia WGS AF: 0.0550 AC: 193 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	5.2
DANN	Benign	0.62

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

Publications

LitVar

Other links and lift over

dbSNP: rs2340693; hg19: chr12-124134988;