chr15-59656979-T-C

Position:

• chr15-59656979-T-C

Variant summary

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

The NM_004492.3(GTF2A2):​c.-50+427A>G variant causes a intron 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_004492.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.424

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GTF2A2	NM_004492.3	c.-50+427A>G		intron_variant		ENST00000396060.7	NP_004483.1
GTF2A2	NM_001320930.2	c.-214A>G		5_prime_UTR_variant	2/6		NP_001307859.1
GTF2A2	NM_001320929.2	c.-50+145A>G		intron_variant			NP_001307858.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GTF2A2	ENST00000396060.7	c.-50+427A>G		intron_variant		1	NM_004492.3	ENSP00000379372	P1
	ENST00000441746.1	n.69-12653A>G		intron_variant, non_coding_transcript_variant		3

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

Gnomad4 FIN exome AF: 0.500

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

Gnomad4 AFR AF: 0.165

Gnomad4 AMR AF: 0.388

Gnomad4 ASJ AF: 0.423

Gnomad4 EAS AF: 0.583

Gnomad4 SAS AF: 0.378

Gnomad4 FIN AF: 0.412

Gnomad4 NFE AF: 0.346

Gnomad4 OTH AF: 0.329

Alfa AF: 0.341 Hom.: 4355

Bravo AF: 0.312

Asia WGS AF: 0.456 AC: 1586 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	12
DANN	Benign	0.85

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: rs8041394; hg19: chr15-59949178;