8-70422254-A-G

Variant names:

• chr8-70422254-A-G
• rs7823221
• XM_047421240.1:c.-77+34137T>C

Variant summary

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

The XM_047421240.1(NCOA2):​c.-77+34137T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.384 in 151,986 control chromosomes in the GnomAD database, including 11,620 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 0.38 (11620 hom., cov: 31)
• Consequence: NCOA2 XM_047421240.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.42
• Publications: 2 publications found

Genes affected

NCOA2 (HGNC:7669): (nuclear receptor coactivator 2) The protein encoded by this gene functions as a transcriptional coactivator for nuclear hormone receptors, including steroid, thyroid, retinoid, and vitamin D receptors. The encoded protein acts as an intermediary factor for the ligand-dependent activity of these nuclear receptors, which regulate their target genes upon binding of cognate response elements. This gene has been found to be involved in translocations that result in fusions with other genes in various cancers, including the lysine acetyltransferase 6A (KAT6A) gene in acute myeloid leukemia, the ETS variant 6 (ETV6) gene in acute lymphoblastic leukemia, and the hes related family bHLH transcription factor with YRPW motif 1 (HEY1) gene in mesenchymal chondrosarcoma. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2016]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.08).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.558 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NCOA2	XM_047421240.1	c.-77+34137T>C		intron_variant	Intron 1 of 22		XP_047277196.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD3 genomes AF: 0.384 AC: 58312 AN: 151868 Hom.: 11614 Cov.: 31

Gnomad AFR AF: 0.450

Gnomad AMI AF: 0.182

Gnomad AMR AF: 0.294

Gnomad ASJ AF: 0.499

Gnomad EAS AF: 0.531

Gnomad SAS AF: 0.576

Gnomad FIN AF: 0.325

Gnomad MID AF: 0.424

Gnomad NFE AF: 0.345

Gnomad OTH AF: 0.380

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.384 AC: 58346 AN: 151986 Hom.: 11620 Cov.: 31 AF XY: 0.385 AC XY: 28592 AN XY: 74264

African (AFR) AF: 0.449 AC: 18611 AN: 41424

American (AMR) AF: 0.294 AC: 4488 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.499 AC: 1730 AN: 3468

East Asian (EAS) AF: 0.531 AC: 2749 AN: 5174

South Asian (SAS) AF: 0.576 AC: 2774 AN: 4814

European-Finnish (FIN) AF: 0.325 AC: 3422 AN: 10536

Middle Eastern (MID) AF: 0.429 AC: 126 AN: 294

European-Non Finnish (NFE) AF: 0.345 AC: 23480 AN: 67974

Other (OTH) AF: 0.379 AC: 800 AN: 2112

Alfa AF: 0.361 Hom.: 42479

Bravo AF: 0.376

Asia WGS AF: 0.521 AC: 1811 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.046
DANN	Benign	0.34
PhyloP100		-2.4

Splicing

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

Other links and lift over

dbSNP: rs7823221; hg19: chr8-71334489;