rs447978

Variant names:

• chr3-120772239-G-A
• rs447978
• NM_005513.3:c.650+1310G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 8 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
GTF2E1	NM_005513.3	c.650+1310G>A		intron_variant	Intron 3 of 4	ENST00000283875.6	NP_005504.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GTF2E1	ENST00000283875.6	c.650+1310G>A		intron_variant	Intron 3 of 4	1	NM_005513.3	ENSP00000283875.5
GTF2E1	ENST00000469772.5	c.149+1310G>A		intron_variant	Intron 2 of 2	5		ENSP00000418808.1

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

African (AFR) AF: 0.860 AC: 35679 AN: 41476

American (AMR) AF: 0.773 AC: 11793 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.560 AC: 1942 AN: 3468

East Asian (EAS) AF: 0.972 AC: 5026 AN: 5170

South Asian (SAS) AF: 0.584 AC: 2817 AN: 4826

European-Finnish (FIN) AF: 0.748 AC: 7913 AN: 10576

Middle Eastern (MID) AF: 0.592 AC: 174 AN: 294

European-Non Finnish (NFE) AF: 0.665 AC: 45142 AN: 67922

Other (OTH) AF: 0.692 AC: 1458 AN: 2108

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
PhyloP100		-0.28
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs447978; hg19: chr3-120491086;