rs6094753

Positions:

• chr20-47630030-G-A

Variant summary

Our verdict is Benign. Variant got -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

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.554 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NCOA3	NM_181659.3	c.823+2007G>A		intron_variant		ENST00000371998.8
NCOA3	NM_001174087.2	c.823+2007G>A		intron_variant
NCOA3	NM_001174088.2	c.823+2007G>A		intron_variant
NCOA3	NM_006534.4	c.823+2007G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NCOA3	ENST00000371998.8	c.823+2007G>A		intron_variant		1	NM_181659.3	P4
NCOA3	ENST00000371997.3	c.823+2007G>A		intron_variant		1		A2
NCOA3	ENST00000372004.7	c.823+2007G>A		intron_variant		1		A2

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

Gnomad4 AFR AF: 0.560

Gnomad4 AMR AF: 0.386

Gnomad4 ASJ AF: 0.567

Gnomad4 EAS AF: 0.323

Gnomad4 SAS AF: 0.340

Gnomad4 FIN AF: 0.323

Gnomad4 NFE AF: 0.453

Gnomad4 OTH AF: 0.491

Alfa AF: 0.455 Hom.: 2577

Bravo AF: 0.470

Asia WGS AF: 0.346 AC: 1209 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.6
DANN	Benign	0.31

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: rs6094753; hg19: chr20-46258774;