20-46068792-T-G

Variant names:

• chr20-46068792-T-G
• rs3092502
• NM_020967.3:c.366-154A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020967.3(NCOA5):​c.366-154A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.646 in 152,060 control chromosomes in the GnomAD database, including 33,496 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 0.65 (33496 hom., cov: 32)
• Consequence: NCOA5 NM_020967.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.247
• Publications: 5 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.869 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020967.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NCOA5	NM_020967.3	MANE Select	c.366-154A>C		intron	N/A	NP_066018.1
	NCOA5	NM_001348148.2		c.51-154A>C		intron	N/A	NP_001335077.1
	NCOA5	NM_001348149.2		c.366-154A>C		intron	N/A	NP_001335078.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NCOA5	ENST00000290231.11	TSL:1 MANE Select	c.366-154A>C		intron	N/A	ENSP00000290231.6
	NCOA5	ENST00000372291.3	TSL:3	c.51-154A>C		intron	N/A	ENSP00000361365.3

Frequencies

GnomAD3 genomes AF: 0.645 AC: 98058 AN: 151942 Hom.: 33428 Cov.: 32

Gnomad AFR AF: 0.877

Gnomad AMI AF: 0.595

Gnomad AMR AF: 0.664

Gnomad ASJ AF: 0.531

Gnomad EAS AF: 0.597

Gnomad SAS AF: 0.667

Gnomad FIN AF: 0.476

Gnomad MID AF: 0.589

Gnomad NFE AF: 0.536

Gnomad OTH AF: 0.615

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

GnomAD4 genome AF: 0.646 AC: 98188 AN: 152060 Hom.: 33496 Cov.: 32 AF XY: 0.642 AC XY: 47692 AN XY: 74310

African (AFR) AF: 0.877 AC: 36392 AN: 41496

American (AMR) AF: 0.665 AC: 10155 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.531 AC: 1844 AN: 3470

East Asian (EAS) AF: 0.598 AC: 3090 AN: 5170

South Asian (SAS) AF: 0.665 AC: 3202 AN: 4812

European-Finnish (FIN) AF: 0.476 AC: 5022 AN: 10550

Middle Eastern (MID) AF: 0.582 AC: 171 AN: 294

European-Non Finnish (NFE) AF: 0.536 AC: 36456 AN: 67962

Other (OTH) AF: 0.621 AC: 1313 AN: 2116

Alfa AF: 0.440 Hom.: 1095

Bravo AF: 0.669

Asia WGS AF: 0.686 AC: 2389 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.7
DANN	Benign	0.84
PhyloP100		-0.25
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: rs3092502; hg19: chr20-44697431;