20-47604780-C-G

Variant names:

• chr20-47604780-C-G
• rs10485463
• NM_181659.3:c.-19-17449C>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.-19-17449C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.206 in 152,108 control chromosomes in the GnomAD database, including 3,755 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 0.21 (3755 hom., cov: 33)
• Consequence: NCOA3 NM_181659.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.338
• Publications: 2 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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.266 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NCOA3	NM_181659.3	c.-19-17449C>G		intron_variant	Intron 2 of 22	ENST00000371998.8	NP_858045.1
NCOA3	NM_001174087.2	c.-19-17449C>G		intron_variant	Intron 2 of 22		NP_001167558.1
NCOA3	NM_006534.4	c.-19-17449C>G		intron_variant	Intron 2 of 22		NP_006525.2
NCOA3	NM_001174088.2	c.-19-17449C>G		intron_variant	Intron 2 of 22		NP_001167559.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NCOA3	ENST00000371998.8	c.-19-17449C>G		intron_variant	Intron 2 of 22	1	NM_181659.3	ENSP00000361066.3
NCOA3	ENST00000372004.7	c.-19-17449C>G		intron_variant	Intron 2 of 22	1		ENSP00000361073.1
NCOA3	ENST00000371997.3	c.-19-17449C>G		intron_variant	Intron 2 of 22	1		ENSP00000361065.3

Frequencies

GnomAD3 genomes AF: 0.207 AC: 31400 AN: 151988 Hom.: 3759 Cov.: 33

Gnomad AFR AF: 0.0879

Gnomad AMI AF: 0.450

Gnomad AMR AF: 0.209

Gnomad ASJ AF: 0.335

Gnomad EAS AF: 0.217

Gnomad SAS AF: 0.253

Gnomad FIN AF: 0.170

Gnomad MID AF: 0.309

Gnomad NFE AF: 0.269

Gnomad OTH AF: 0.238

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

GnomAD4 genome AF: 0.206 AC: 31409 AN: 152108 Hom.: 3755 Cov.: 33 AF XY: 0.204 AC XY: 15187 AN XY: 74348

African (AFR) AF: 0.0879 AC: 3650 AN: 41530

American (AMR) AF: 0.209 AC: 3184 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.335 AC: 1162 AN: 3468

East Asian (EAS) AF: 0.217 AC: 1123 AN: 5174

South Asian (SAS) AF: 0.252 AC: 1215 AN: 4818

European-Finnish (FIN) AF: 0.170 AC: 1794 AN: 10564

Middle Eastern (MID) AF: 0.313 AC: 92 AN: 294

European-Non Finnish (NFE) AF: 0.269 AC: 18275 AN: 67970

Other (OTH) AF: 0.239 AC: 504 AN: 2110

Alfa AF: 0.211 Hom.: 453

Bravo AF: 0.205

Asia WGS AF: 0.212 AC: 741 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.65
DANN	Benign	0.34
PhyloP100		0.34
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: rs10485463; hg19: chr20-46233524;