15-59657691-T-G

Variant names:

• chr15-59657691-T-G
• rs1871500
• ENST00000441746.1:n.69-13365A>C

Variant summary

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

The ENST00000441746.1(ENSG00000227161):​n.69-13365A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.653 in 152,192 control chromosomes in the GnomAD database, including 32,832 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 0.65 (32826 hom., cov: 34)
  • Exomes 𝑓: 0.59 (6 hom.)
• Consequence: ENSG00000227161 ENST00000441746.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.60

Genes affected

ENSG00000227161 (HGNC:):

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.721 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GTF2A2	NM_004492.3	c.-335A>C		upstream_gene_variant		ENST00000396060.7	NP_004483.1
GTF2A2	NM_001320930.2	c.-554A>C		upstream_gene_variant			NP_001307859.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GTF2A2	ENST00000396060.7	c.-335A>C		upstream_gene_variant		1	NM_004492.3	ENSP00000379372.2

Frequencies

GnomAD3 genomes AF: 0.653 AC: 99342 AN: 152042 Hom.: 32790 Cov.: 34

Gnomad AFR AF: 0.728

Gnomad AMI AF: 0.702

Gnomad AMR AF: 0.602

Gnomad ASJ AF: 0.573

Gnomad EAS AF: 0.417

Gnomad SAS AF: 0.623

Gnomad FIN AF: 0.587

Gnomad MID AF: 0.687

Gnomad NFE AF: 0.654

Gnomad OTH AF: 0.644

GnomAD4 exome AF: 0.594 AC: 19 AN: 32 Hom.: 6 AF XY: 0.667 AC XY: 16 AN XY: 24

Gnomad4 AFR exome AF: 0.500

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.625

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.654 AC: 99437 AN: 152160 Hom.: 32826 Cov.: 34 AF XY: 0.648 AC XY: 48189 AN XY: 74386

Gnomad4 AFR AF: 0.728

Gnomad4 AMR AF: 0.602

Gnomad4 ASJ AF: 0.573

Gnomad4 EAS AF: 0.417

Gnomad4 SAS AF: 0.622

Gnomad4 FIN AF: 0.587

Gnomad4 NFE AF: 0.654

Gnomad4 OTH AF: 0.644

Alfa AF: 0.635 Hom.: 12302

Bravo AF: 0.653

Asia WGS AF: 0.535 AC: 1859 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.44
DANN	Benign	0.42

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1871500; hg19: chr15-59949890;