rs2076548

Positions:

• chr20-47639264-A-G

Variant summary

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

The NM_181659.3(NCOA3):​c.2707+62A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0902 in 1,355,830 control chromosomes in the GnomAD database, including 6,797 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 0.13 (1724 hom., cov: 32)
  • Exomes 𝑓: 0.086 (5073 hom.)
• Consequence: NCOA3 NM_181659.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.825

Genes affected

NCOA3 (HGNC:7670): (nuclear receptor coactivator 3) The protein encoded by this gene is a nuclear receptor coactivator that interacts with nuclear hormone receptors to enhance their transcriptional activator functions. The encoded protein has histone acetyltransferase activity and recruits p300/CBP-associated factor and CREB binding protein as part of a multisubunit coactivation complex. This protein is initially found in the cytoplasm but is translocated into the nucleus upon phosphorylation. Several transcript variants encoding different isoforms have been found for this gene. In addition, a polymorphic repeat region is found in the C-terminus of the encoded protein. [provided by RefSeq, Mar 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.235 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NCOA3	NM_181659.3	c.2707+62A>G		intron_variant		ENST00000371998.8	NP_858045.1
NCOA3	NM_001174087.2	c.2707+62A>G		intron_variant			NP_001167558.1
NCOA3	NM_006534.4	c.2707+62A>G		intron_variant			NP_006525.2
NCOA3	NM_001174088.2	c.2737+62A>G		intron_variant			NP_001167559.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NCOA3	ENST00000371998.8	c.2707+62A>G		intron_variant		1	NM_181659.3	ENSP00000361066.3
NCOA3	ENST00000372004.7	c.2707+62A>G		intron_variant		1		ENSP00000361073.1
NCOA3	ENST00000371997.3	c.2737+62A>G		intron_variant		1		ENSP00000361065.3

Frequencies

GnomAD3 genomes AF: 0.128 AC: 19410 AN: 152160 Hom.: 1724 Cov.: 32

Gnomad AFR AF: 0.239

Gnomad AMI AF: 0.117

Gnomad AMR AF: 0.0859

Gnomad ASJ AF: 0.123

Gnomad EAS AF: 0.0832

Gnomad SAS AF: 0.114

Gnomad FIN AF: 0.0521

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.0851

Gnomad OTH AF: 0.133

GnomAD4 exome AF: 0.0855 AC: 102910 AN: 1203552 Hom.: 5073 AF XY: 0.0867 AC XY: 52389 AN XY: 604262

Gnomad4 AFR exome AF: 0.245

Gnomad4 AMR exome AF: 0.0650

Gnomad4 ASJ exome AF: 0.121

Gnomad4 EAS exome AF: 0.104

Gnomad4 SAS exome AF: 0.108

Gnomad4 FIN exome AF: 0.0531

Gnomad4 NFE exome AF: 0.0788

Gnomad4 OTH exome AF: 0.0970

GnomAD4 genome AF: 0.127 AC: 19415 AN: 152278 Hom.: 1724 Cov.: 32 AF XY: 0.125 AC XY: 9279 AN XY: 74476

Gnomad4 AFR AF: 0.239

Gnomad4 AMR AF: 0.0856

Gnomad4 ASJ AF: 0.123

Gnomad4 EAS AF: 0.0830

Gnomad4 SAS AF: 0.114

Gnomad4 FIN AF: 0.0521

Gnomad4 NFE AF: 0.0851

Gnomad4 OTH AF: 0.132

Alfa AF: 0.108 Hom.: 157

Bravo AF: 0.133

Asia WGS AF: 0.117 AC: 408 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	4.6
DANN	Benign	0.44

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: rs2076548; hg19: chr20-46268008;