rs2076548

Variant names:

• chr20-47639264-A-G
• rs2076548
• NM_181659.3:c.2707+62A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
NCOA3	NM_181659.3	c.2707+62A>G		intron_variant	Intron 14 of 22	ENST00000371998.8	NP_858045.1
NCOA3	NM_001174087.2	c.2707+62A>G		intron_variant	Intron 14 of 22		NP_001167558.1
NCOA3	NM_006534.4	c.2707+62A>G		intron_variant	Intron 14 of 22		NP_006525.2
NCOA3	NM_001174088.2	c.2737+62A>G		intron_variant	Intron 14 of 22		NP_001167559.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NCOA3	ENST00000371998.8	c.2707+62A>G		intron_variant	Intron 14 of 22	1	NM_181659.3	ENSP00000361066.3
NCOA3	ENST00000372004.7	c.2707+62A>G		intron_variant	Intron 14 of 22	1		ENSP00000361073.1
NCOA3	ENST00000371997.3	c.2737+62A>G		intron_variant	Intron 14 of 22	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

African (AFR) AF: 0.245 AC: 6646 AN: 27146

American (AMR) AF: 0.0650 AC: 2340 AN: 36002

Ashkenazi Jewish (ASJ) AF: 0.121 AC: 2633 AN: 21678

East Asian (EAS) AF: 0.104 AC: 3954 AN: 37904

South Asian (SAS) AF: 0.108 AC: 7794 AN: 71912

European-Finnish (FIN) AF: 0.0531 AC: 2725 AN: 51308

Middle Eastern (MID) AF: 0.158 AC: 805 AN: 5096

European-Non Finnish (NFE) AF: 0.0788 AC: 71043 AN: 901276

Other (OTH) AF: 0.0970 AC: 4970 AN: 51230

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

African (AFR) AF: 0.239 AC: 9914 AN: 41528

American (AMR) AF: 0.0856 AC: 1311 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.123 AC: 428 AN: 3470

East Asian (EAS) AF: 0.0830 AC: 431 AN: 5190

South Asian (SAS) AF: 0.114 AC: 550 AN: 4828

European-Finnish (FIN) AF: 0.0521 AC: 553 AN: 10620

Middle Eastern (MID) AF: 0.184 AC: 54 AN: 294

European-Non Finnish (NFE) AF: 0.0851 AC: 5788 AN: 68016

Other (OTH) AF: 0.132 AC: 279 AN: 2110

Alfa AF: 0.113 Hom.: 177

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
PhyloP100		0.82
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2076548; hg19: chr20-46268008;