rs447978

chr3-120772239-G-A

Variant summary

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

The NM_005513.3(GTF2E1):c.650+1310G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.74 in 152,010 control chromosomes in the GnomAD database, including 42,525 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 0.74 (42525 hom., cov: 32)
• Consequence: GTF2E1 NM_005513.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.280

Genes affected

GTF2E1 (HGNC:4650): (general transcription factor IIE subunit 1) Enables RNA polymerase II general transcription initiation factor activity. Involved in transcription by RNA polymerase II. Located in cytosol and nucleoplasm. Part of transcription factor TFIID complex and transcription preinitiation complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.95 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GTF2E1	NM_005513.3	c.650+1310G>A		intron_variant		ENST00000283875.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GTF2E1	ENST00000283875.6	c.650+1310G>A		intron_variant		1	NM_005513.3	P1
GTF2E1	ENST00000469772.5	c.149+1310G>A		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.740 AC: 112362 AN: 151892 Hom.: 42467 Cov.: 32

Gnomad AFR AF: 0.860

Gnomad AMI AF: 0.591

Gnomad AMR AF: 0.773

Gnomad ASJ AF: 0.560

Gnomad EAS AF: 0.972

Gnomad SAS AF: 0.582

Gnomad FIN AF: 0.748

Gnomad MID AF: 0.589

Gnomad NFE AF: 0.665

Gnomad OTH AF: 0.696

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

GnomAD4 genome AF: 0.740 AC: 112483 AN: 152010 Hom.: 42525 Cov.: 32 AF XY: 0.743 AC XY: 55226 AN XY: 74314

Gnomad4 AFR AF: 0.860

Gnomad4 AMR AF: 0.773

Gnomad4 ASJ AF: 0.560

Gnomad4 EAS AF: 0.972

Gnomad4 SAS AF: 0.584

Gnomad4 FIN AF: 0.748

Gnomad4 NFE AF: 0.665

Gnomad4 OTH AF: 0.692

Alfa AF: 0.710 Hom.: 7395

Bravo AF: 0.752

Asia WGS AF: 0.744 AC: 2585 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	0.48
Dann	Benign	0.18

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: rs447978; hg19: chr3-120491086;