Genetic Variant NCOA5:c.630-80A>G (chr20-46065308-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_020967.3(NCOA5):c.630-80A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.253 in 1,370,774 control chromosomes in the GnomAD database, including 45,365 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 0.22 ( 3975 hom., cov: 32)

Exomes 𝑓: 0.26 ( 41390 hom. )

Consequence

NCOA5
NM_020967.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.471

Publications

13 publications found

Variant links:

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]

NCOA5 links:

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ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.32 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NCOA5	NM_020967.3 link	c.630-80A>G		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 link	c.630-80A>G		intron_variant	Intron 5 of 7	1	NM_020967.3	ENSP00000290231.6		Q9HCD5

Frequencies

GnomAD3 genomes

AF:

0.221

AC:

33544

AN:

152032

Hom.:

3978

Cov.:

show subpopulations

Gnomad AFR

AF:

0.126

Gnomad AMI

AF:

0.254

Gnomad AMR

AF:

0.220

Gnomad ASJ

AF:

0.301

Gnomad EAS

AF:

0.333

Gnomad SAS

AF:

0.227

Gnomad FIN

AF:

0.217

Gnomad MID

AF:

0.345

Gnomad NFE

AF:

0.264

Gnomad OTH

AF:

0.252

GnomAD4 exome

AF:

0.257

AC:

313534

AN:

1218624

Hom.:

41390

AF XY:

0.258

AC XY:

158852

AN XY:

616650

show subpopulations

African (AFR)

AF:

0.120

AC:

3465

AN:

28792

American (AMR)

AF:

0.170

AC:

7389

AN:

43540

Ashkenazi Jewish (ASJ)

AF:

0.295

AC:

7019

AN:

23768

East Asian (EAS)

AF:

0.336

AC:

12901

AN:

38442

South Asian (SAS)

AF:

0.230

AC:

18254

AN:

79432

European-Finnish (FIN)

AF:

0.230

AC:

11480

AN:

49972

Middle Eastern (MID)

AF:

0.281

AC:

1385

AN:

4926

European-Non Finnish (NFE)

AF:

0.265

AC:

238196

AN:

897408

Other (OTH)

AF:

0.257

AC:

13445

AN:

52344

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

12362

24723

37085

49446

61808

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7288

14576

21864

29152

36440

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.220

AC:

33540

AN:

152150

Hom.:

3975

Cov.:

AF XY:

0.218

AC XY:

16219

AN XY:

74372

show subpopulations

African (AFR)

AF:

0.126

AC:

5216

AN:

41516

American (AMR)

AF:

0.220

AC:

3359

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.301

AC:

1042

AN:

3466

East Asian (EAS)

AF:

0.333

AC:

1722

AN:

5172

South Asian (SAS)

AF:

0.227

AC:

1096

AN:

4824

European-Finnish (FIN)

AF:

0.217

AC:

2297

AN:

10586

Middle Eastern (MID)

AF:

0.330

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.264

AC:

17952

AN:

67980

Other (OTH)

AF:

0.250

AC:

528

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1323

2646

3969

5292

6615

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

354

708

1062

1416

1770

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.248

Hom.:

5147

Bravo

AF:

0.217

Asia WGS

AF:

0.240

AC:

837

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.43

(source)

DANN

Benign

0.34

PhyloP100

-0.47

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over