rs6018600

Variant names:

• chr20-47629833-A-G
• rs6018600
• NM_181659.3:c.823+1810A>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.823+1810A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.572 in 152,070 control chromosomes in the GnomAD database, including 25,304 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 0.57 (25304 hom., cov: 32)
• Consequence: NCOA3 NM_181659.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.490
• Publications: 4 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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.625 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_181659.3. 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
	NCOA3	NM_181659.3	MANE Select	c.823+1810A>G		intron	N/A	NP_858045.1
	NCOA3	NM_001174087.2		c.823+1810A>G		intron	N/A	NP_001167558.1
	NCOA3	NM_006534.4		c.823+1810A>G		intron	N/A	NP_006525.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NCOA3	ENST00000371998.8	TSL:1 MANE Select	c.823+1810A>G		intron	N/A	ENSP00000361066.3
	NCOA3	ENST00000372004.7	TSL:1	c.823+1810A>G		intron	N/A	ENSP00000361073.1
	NCOA3	ENST00000371997.3	TSL:1	c.823+1810A>G		intron	N/A	ENSP00000361065.3

Frequencies

GnomAD3 genomes AF: 0.572 AC: 86844 AN: 151952 Hom.: 25275 Cov.: 32

Gnomad AFR AF: 0.631

Gnomad AMI AF: 0.703

Gnomad AMR AF: 0.478

Gnomad ASJ AF: 0.717

Gnomad EAS AF: 0.390

Gnomad SAS AF: 0.481

Gnomad FIN AF: 0.494

Gnomad MID AF: 0.703

Gnomad NFE AF: 0.577

Gnomad OTH AF: 0.610

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

GnomAD4 genome AF: 0.572 AC: 86921 AN: 152070 Hom.: 25304 Cov.: 32 AF XY: 0.567 AC XY: 42128 AN XY: 74320

African (AFR) AF: 0.632 AC: 26201 AN: 41472

American (AMR) AF: 0.478 AC: 7301 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.717 AC: 2488 AN: 3468

East Asian (EAS) AF: 0.390 AC: 2018 AN: 5170

South Asian (SAS) AF: 0.479 AC: 2312 AN: 4826

European-Finnish (FIN) AF: 0.494 AC: 5211 AN: 10552

Middle Eastern (MID) AF: 0.701 AC: 206 AN: 294

European-Non Finnish (NFE) AF: 0.577 AC: 39253 AN: 67980

Other (OTH) AF: 0.610 AC: 1291 AN: 2116

Alfa AF: 0.583 Hom.: 68156

Bravo AF: 0.572

Asia WGS AF: 0.457 AC: 1591 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	2.0
DANN	Benign	0.79
PhyloP100		-0.49
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: rs6018600; hg19: chr20-46258577;