rs2425752

Positions:

• chr20-46073481-T-C
• chr20-46073481-T-G

Variant summary

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

The NM_020967.3(NCOA5):​c.39-2945A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.79 in 152,194 control chromosomes in the GnomAD database, including 48,323 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 0.79 (48323 hom., cov: 32)
• Consequence: NCOA5 NM_020967.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.853

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.939 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NCOA5	NM_020967.3	c.39-2945A>G		intron_variant		ENST00000290231.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NCOA5	ENST00000290231.11	c.39-2945A>G		intron_variant		1	NM_020967.3	P1
NCOA5	ENST00000372291.3	c.-277-2945A>G		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.790 AC: 120175 AN: 152076 Hom.: 48255 Cov.: 32

Gnomad AFR AF: 0.947

Gnomad AMI AF: 0.761

Gnomad AMR AF: 0.774

Gnomad ASJ AF: 0.704

Gnomad EAS AF: 0.630

Gnomad SAS AF: 0.757

Gnomad FIN AF: 0.710

Gnomad MID AF: 0.742

Gnomad NFE AF: 0.731

Gnomad OTH AF: 0.769

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

GnomAD4 genome AF: 0.790 AC: 120304 AN: 152194 Hom.: 48323 Cov.: 32 AF XY: 0.785 AC XY: 58438 AN XY: 74400

Gnomad4 AFR AF: 0.947

Gnomad4 AMR AF: 0.775

Gnomad4 ASJ AF: 0.704

Gnomad4 EAS AF: 0.630

Gnomad4 SAS AF: 0.756

Gnomad4 FIN AF: 0.710

Gnomad4 NFE AF: 0.731

Gnomad4 OTH AF: 0.772

Alfa AF: 0.744 Hom.: 27210

Bravo AF: 0.803

Asia WGS AF: 0.756 AC: 2630 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.3
DANN	Benign	0.65

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: rs2425752; hg19: chr20-44702120;