20-47581409-C-T

Position:

• chr20-47581409-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_181659.3(NCOA3):​c.-98-1774C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.292 in 151,980 control chromosomes in the GnomAD database, including 7,151 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 0.29 (7151 hom., cov: 32)
• Consequence: NCOA3 NM_181659.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.184

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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.567 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NCOA3	NM_181659.3	c.-98-1774C>T		intron_variant		ENST00000371998.8
NCOA3	NM_001174087.2	c.-98-1774C>T		intron_variant
NCOA3	NM_001174088.2	c.-98-1774C>T		intron_variant
NCOA3	NM_006534.4	c.-98-1774C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NCOA3	ENST00000371998.8	c.-98-1774C>T		intron_variant		1	NM_181659.3	P4
NCOA3	ENST00000371997.3	c.-98-1774C>T		intron_variant		1		A2
NCOA3	ENST00000372004.7	c.-98-1774C>T		intron_variant		1		A2

Frequencies

GnomAD3 genomes AF: 0.292 AC: 44397 AN: 151862 Hom.: 7144 Cov.: 32

Gnomad AFR AF: 0.245

Gnomad AMI AF: 0.153

Gnomad AMR AF: 0.396

Gnomad ASJ AF: 0.181

Gnomad EAS AF: 0.584

Gnomad SAS AF: 0.431

Gnomad FIN AF: 0.386

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.261

Gnomad OTH AF: 0.256

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

GnomAD4 genome AF: 0.292 AC: 44423 AN: 151980 Hom.: 7151 Cov.: 32 AF XY: 0.303 AC XY: 22514 AN XY: 74258

Gnomad4 AFR AF: 0.244

Gnomad4 AMR AF: 0.397

Gnomad4 ASJ AF: 0.181

Gnomad4 EAS AF: 0.584

Gnomad4 SAS AF: 0.431

Gnomad4 FIN AF: 0.386

Gnomad4 NFE AF: 0.261

Gnomad4 OTH AF: 0.257

Alfa AF: 0.272 Hom.: 3797

Bravo AF: 0.293

Asia WGS AF: 0.468 AC: 1623 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.97
DANN	Benign	0.46

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs6066394; hg19: chr20-46210153;