rs1950174

Positions:

• chr20-46085765-C-A

Variant summary

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

The NM_020967.3(NCOA5):​c.-30+4052G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.188 in 151,942 control chromosomes in the GnomAD database, including 2,850 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 0.19 (2850 hom., cov: 32)
• Consequence: NCOA5 NM_020967.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.151

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=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.276 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NCOA5	NM_020967.3	c.-30+4052G>T		intron_variant		ENST00000290231.11	NP_066018.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NCOA5	ENST00000290231.11	c.-30+4052G>T		intron_variant		1	NM_020967.3	ENSP00000290231.6
NCOA5	ENST00000372291.3	c.-278+4052G>T		intron_variant		3		ENSP00000361365.3

Frequencies

GnomAD3 genomes AF: 0.188 AC: 28496 AN: 151824 Hom.: 2845 Cov.: 32

Gnomad AFR AF: 0.149

Gnomad AMI AF: 0.276

Gnomad AMR AF: 0.197

Gnomad ASJ AF: 0.193

Gnomad EAS AF: 0.0278

Gnomad SAS AF: 0.290

Gnomad FIN AF: 0.211

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.209

Gnomad OTH AF: 0.171

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

GnomAD4 genome AF: 0.188 AC: 28523 AN: 151942 Hom.: 2850 Cov.: 32 AF XY: 0.189 AC XY: 14031 AN XY: 74250

Gnomad4 AFR AF: 0.149

Gnomad4 AMR AF: 0.197

Gnomad4 ASJ AF: 0.193

Gnomad4 EAS AF: 0.0277

Gnomad4 SAS AF: 0.289

Gnomad4 FIN AF: 0.211

Gnomad4 NFE AF: 0.209

Gnomad4 OTH AF: 0.174

Alfa AF: 0.204 Hom.: 602

Bravo AF: 0.180

Asia WGS AF: 0.161 AC: 560 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	5.0
DANN	Benign	0.63

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: rs1950174; hg19: chr20-44714404;