rs6094753

Variant names:

• chr20-47630030-G-A
• rs6094753
• NM_181659.3:c.823+2007G>A

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+2007G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.462 in 151,944 control chromosomes in the GnomAD database, including 16,824 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 0.46 (16824 hom., cov: 32)
• Consequence: NCOA3 NM_181659.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.622
• Publications: 1 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]

ENSG00000229853 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.554 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+2007G>A		intron	N/A	NP_858045.1
	NCOA3	NM_001174087.2		c.823+2007G>A		intron	N/A	NP_001167558.1
	NCOA3	NM_006534.4		c.823+2007G>A		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+2007G>A		intron	N/A	ENSP00000361066.3
	NCOA3	ENST00000372004.7	TSL:1	c.823+2007G>A		intron	N/A	ENSP00000361073.1
	NCOA3	ENST00000371997.3	TSL:1	c.823+2007G>A		intron	N/A	ENSP00000361065.3

Frequencies

GnomAD3 genomes AF: 0.462 AC: 70181 AN: 151826 Hom.: 16798 Cov.: 32

Gnomad AFR AF: 0.559

Gnomad AMI AF: 0.582

Gnomad AMR AF: 0.387

Gnomad ASJ AF: 0.567

Gnomad EAS AF: 0.324

Gnomad SAS AF: 0.341

Gnomad FIN AF: 0.323

Gnomad MID AF: 0.589

Gnomad NFE AF: 0.453

Gnomad OTH AF: 0.493

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

GnomAD4 genome AF: 0.462 AC: 70253 AN: 151944 Hom.: 16824 Cov.: 32 AF XY: 0.454 AC XY: 33722 AN XY: 74252

African (AFR) AF: 0.560 AC: 23177 AN: 41408

American (AMR) AF: 0.386 AC: 5899 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.567 AC: 1969 AN: 3470

East Asian (EAS) AF: 0.323 AC: 1673 AN: 5172

South Asian (SAS) AF: 0.340 AC: 1639 AN: 4816

European-Finnish (FIN) AF: 0.323 AC: 3402 AN: 10540

Middle Eastern (MID) AF: 0.585 AC: 172 AN: 294

European-Non Finnish (NFE) AF: 0.453 AC: 30758 AN: 67948

Other (OTH) AF: 0.491 AC: 1033 AN: 2102

Alfa AF: 0.457 Hom.: 2680

Bravo AF: 0.470

Asia WGS AF: 0.346 AC: 1209 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.6
DANN	Benign	0.31
PhyloP100		0.62
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: rs6094753; hg19: chr20-46258774;