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

Variant names:

• chr20-46065929-T-A
• rs4812989
• NM_020967.3:c.630-701A>T

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>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.031 in 152,240 control chromosomes in the GnomAD database, including 164 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 0.031 (164 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 (AMR) allele frequency at 95% confidence interval = 0.105 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NCOA5	NM_020967.3	c.630-701A>T		intron_variant	Intron 5 of 7	ENST00000290231.11	NP_066018.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NCOA5	ENST00000290231.11	c.630-701A>T		intron_variant	Intron 5 of 7	1	NM_020967.3	ENSP00000290231.6

Frequencies

GnomAD3 genomes AF: 0.0310 AC: 4714 AN: 152122 Hom.: 161 Cov.: 32

Gnomad AFR AF: 0.00826

Gnomad AMI AF: 0.0462

Gnomad AMR AF: 0.108

Gnomad ASJ AF: 0.0521

Gnomad EAS AF: 0.00481

Gnomad SAS AF: 0.0275

Gnomad FIN AF: 0.0268

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0290

Gnomad OTH AF: 0.0359

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

GnomAD4 genome AF: 0.0310 AC: 4721 AN: 152240 Hom.: 164 Cov.: 32 AF XY: 0.0333 AC XY: 2477 AN XY: 74424

African (AFR) AF: 0.00824 AC: 342 AN: 41526

American (AMR) AF: 0.109 AC: 1665 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0521 AC: 181 AN: 3472

East Asian (EAS) AF: 0.00482 AC: 25 AN: 5182

South Asian (SAS) AF: 0.0273 AC: 132 AN: 4828

European-Finnish (FIN) AF: 0.0268 AC: 284 AN: 10596

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.0290 AC: 1970 AN: 68024

Other (OTH) AF: 0.0364 AC: 77 AN: 2114

Alfa AF: 0.00800 Hom.: 3

Bravo AF: 0.0352

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	7.9
DANN	Benign	0.74
PhyloP100		0.11
Mutation Taster		=100/0	polymorphism

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;