rs6065921

chr20-46085871-A-G

Variant summary

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

The NM_020967.3(NCOA5):c.-30+3946T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.136 in 152,224 control chromosomes in the GnomAD database, including 1,763 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 0.14 (1763 hom., cov: 32)
• Consequence: NCOA5 NM_020967.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.405

Genes affected

NCOA5 (HGNC:15909): (nuclear receptor coactivator 5) This gene encodes a coregulator for the alpha and beta estrogen receptors and the orphan nuclear receptor NR1D2. The protein localizes to the nucleus, and is thought to have both coactivator and corepressor functions. Its interaction with nuclear receptors is independent of the AF2 domain on the receptors, which is known to regulate interaction with other coreceptors. Several alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jan 2017]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.188 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NCOA5	NM_020967.3	c.-30+3946T>C		intron_variant		ENST00000290231.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NCOA5	ENST00000290231.11	c.-30+3946T>C		intron_variant		1	NM_020967.3	P1
NCOA5	ENST00000372291.3	c.-278+3946T>C		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.136 AC: 20695 AN: 152106 Hom.: 1763 Cov.: 32

Gnomad AFR AF: 0.0518

Gnomad AMI AF: 0.166

Gnomad AMR AF: 0.102

Gnomad ASJ AF: 0.172

Gnomad EAS AF: 0.0325

Gnomad SAS AF: 0.0640

Gnomad FIN AF: 0.231

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.191

Gnomad OTH AF: 0.147

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

GnomAD4 genome AF: 0.136 AC: 20693 AN: 152224 Hom.: 1763 Cov.: 32 AF XY: 0.134 AC XY: 10007 AN XY: 74412

Gnomad4 AFR AF: 0.0517

Gnomad4 AMR AF: 0.102

Gnomad4 ASJ AF: 0.172

Gnomad4 EAS AF: 0.0326

Gnomad4 SAS AF: 0.0647

Gnomad4 FIN AF: 0.231

Gnomad4 NFE AF: 0.191

Gnomad4 OTH AF: 0.145

Alfa AF: 0.174 Hom.: 878

Bravo AF: 0.125

Asia WGS AF: 0.0580 AC: 202 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	1.1
Dann	Benign	0.23

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: rs6065921; hg19: chr20-44714510;