NM_020967.3:c.630-701A>C

Variant names:

• chr20-46065929-T-G
• rs4812989
• NM_020967.3:c.630-701A>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.630-701A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0256 in 152,236 control chromosomes in the GnomAD database, including 166 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 0.026 (166 hom., cov: 32)
• Consequence: NCOA5 NM_020967.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.113
• Publications: 4 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=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0866 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.630-701A>C		intron	N/A	NP_066018.1
	NCOA5	NM_001348148.2		c.315-701A>C		intron	N/A	NP_001335077.1
	NCOA5	NM_001348149.2		c.630-701A>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.630-701A>C		intron	N/A	ENSP00000290231.6

Frequencies

GnomAD3 genomes AF: 0.0255 AC: 3884 AN: 152118 Hom.: 167 Cov.: 32

Gnomad AFR AF: 0.0891

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00956

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000309

Gnomad OTH AF: 0.0120

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

GnomAD4 genome AF: 0.0256 AC: 3890 AN: 152236 Hom.: 166 Cov.: 32 AF XY: 0.0248 AC XY: 1847 AN XY: 74432

African (AFR) AF: 0.0890 AC: 3696 AN: 41512

American (AMR) AF: 0.00948 AC: 145 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10598

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000309 AC: 21 AN: 68030

Other (OTH) AF: 0.0118 AC: 25 AN: 2114

Alfa AF: 0.00 Hom.: 3

Bravo AF: 0.0293

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	8.0
DANN	Benign	0.59
PhyloP100		0.11
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: rs4812989; hg19: chr20-44694568;