15-59657691-T-G

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 13 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000441746.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GTF2A2	NM_004492.3	MANE Select	c.-335A>C		upstream_gene	N/A	NP_004483.1
	GTF2A2	NM_001320930.2		c.-554A>C		upstream_gene	N/A	NP_001307859.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000227161	ENST00000441746.1	TSL:3	n.69-13365A>C		intron	N/A
	GTF2A2	ENST00000396060.7	TSL:1 MANE Select	c.-335A>C		upstream_gene	N/A	ENSP00000379372.2
	GTF2A2	ENST00000396061.5	TSL:2	c.-617A>C		upstream_gene	N/A	ENSP00000379373.1

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

African (AFR) AF: 0.500 AC: 1 AN: 2

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: 2 AN: 4

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.625 AC: 15 AN: 24

Other (OTH) AF: 0.500 AC: 1 AN: 2

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

African (AFR) AF: 0.728 AC: 30231 AN: 41524

American (AMR) AF: 0.602 AC: 9208 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.573 AC: 1987 AN: 3466

East Asian (EAS) AF: 0.417 AC: 2157 AN: 5174

South Asian (SAS) AF: 0.622 AC: 2999 AN: 4824

European-Finnish (FIN) AF: 0.587 AC: 6206 AN: 10570

Middle Eastern (MID) AF: 0.694 AC: 204 AN: 294

European-Non Finnish (NFE) AF: 0.654 AC: 44444 AN: 67990

Other (OTH) AF: 0.644 AC: 1361 AN: 2112

Alfa AF: 0.635 Hom.: 17383

Bravo AF: 0.653

Asia WGS AF: 0.535 AC: 1859 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.44
DANN	Benign	0.42
PhyloP100		-1.6
PromoterAI		-0.0024	Neutral

Splicing

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

Other links and lift over

dbSNP: rs1871500; hg19: chr15-59949890;