15-59656979-T-C

Variant names:

• chr15-59656979-T-C
• rs8041394
• NM_004492.3:c.-50+427A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001320930.2(GTF2A2):​c.-214A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.316 in 152,144 control chromosomes in the GnomAD database, including 8,432 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 0.32 (8432 hom., cov: 33)
  • Exomes 𝑓: 0.50 (0 hom.)
• Consequence: GTF2A2 NM_001320930.2 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.424
• Publications: 7 publications found

Genes affected

GTF2A2 (HGNC:4647): (general transcription factor IIA subunit 2) Accurate transcription initiation on TATA-containing class II genes involves the ordered assembly of RNA polymerase II (POLR2A; MIM 180660) and the general initiation factors TFIIA, TFIIB (MIM 189963), TFIID (MIM 313650), TFIIE (MIM 189962), TFIIF (MIM 189968), TFIIG/TFIIJ, and TFIIH (MIM 189972). The first step involves recognition of the TATA element by the TATA-binding subunit (TBP; MIM 600075) and may be regulated by TFIIA, a factor that interacts with both TBP and a TBP-associated factor (TAF; MIM 600475) in TFIID. TFIIA has 2 subunits (43 and 12 kD) in yeast and 3 subunits in higher eukaryotes. In HeLa extracts, it consists of a 35-kD alpha subunit and a 19-kD beta subunit encoded by the N- and C-terminal regions of GTF2A1 (MIM 600520), respectively, and a 12-kD gamma subunit encoded by GTF2A2 (DeJong et al., 1995 [PubMed 7724559]).[supplied by OMIM, Mar 2008]

ENSG00000227161 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.566 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001320930.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GTF2A2	NM_004492.3	MANE Select	c.-50+427A>G		intron	N/A	NP_004483.1	P52657
	GTF2A2	NM_001320930.2		c.-214A>G		5_prime_UTR	Exon 2 of 6	NP_001307859.1	P52657
	GTF2A2	NM_001320929.2		c.-50+145A>G		intron	N/A	NP_001307858.1	P52657

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GTF2A2	ENST00000396060.7	TSL:1 MANE Select	c.-50+427A>G		intron	N/A	ENSP00000379372.2	P52657
	GTF2A2	ENST00000396063.5	TSL:2	c.-214A>G		5_prime_UTR	Exon 2 of 6	ENSP00000379375.1	P52657
	GTF2A2	ENST00000933398.1		c.-411A>G		5_prime_UTR	Exon 2 of 7	ENSP00000603457.1

Frequencies

GnomAD3 genomes AF: 0.316 AC: 48056 AN: 152024 Hom.: 8436 Cov.: 33

Gnomad AFR AF: 0.165

Gnomad AMI AF: 0.298

Gnomad AMR AF: 0.389

Gnomad ASJ AF: 0.423

Gnomad EAS AF: 0.584

Gnomad SAS AF: 0.378

Gnomad FIN AF: 0.412

Gnomad MID AF: 0.304

Gnomad NFE AF: 0.346

Gnomad OTH AF: 0.330

GnomAD4 exome AF: 0.500 AC: 1 AN: 2 Hom.: 0 Cov.: 0 AF XY: 0.500 AC XY: 1 AN XY: 2

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.500 AC: 1 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.316 AC: 48059 AN: 152142 Hom.: 8432 Cov.: 33 AF XY: 0.323 AC XY: 24005 AN XY: 74346

African (AFR) AF: 0.165 AC: 6867 AN: 41548

American (AMR) AF: 0.388 AC: 5934 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.423 AC: 1469 AN: 3470

East Asian (EAS) AF: 0.583 AC: 3016 AN: 5170

South Asian (SAS) AF: 0.378 AC: 1821 AN: 4814

European-Finnish (FIN) AF: 0.412 AC: 4344 AN: 10548

Middle Eastern (MID) AF: 0.296 AC: 87 AN: 294

European-Non Finnish (NFE) AF: 0.346 AC: 23554 AN: 67988

Other (OTH) AF: 0.329 AC: 695 AN: 2110

Alfa AF: 0.342 Hom.: 4861

Bravo AF: 0.312

Asia WGS AF: 0.456 AC: 1586 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	12
DANN	Benign	0.85
PhyloP100		0.42
PromoterAI		0.025	Neutral
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: rs8041394; hg19: chr15-59949178;