dbSNP rs2903908: NCOA5:c.630-80A>G (chr20-46065308-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -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

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 made for transcript

Verdict is Benign. Variant got -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

Gnomad4 AFR exome

AF:

0.120

Gnomad4 AMR exome

AF:

0.170

Gnomad4 ASJ exome

AF:

0.295

Gnomad4 EAS exome

AF:

0.336

Gnomad4 SAS exome

AF:

0.230

Gnomad4 FIN exome

AF:

0.230

Gnomad4 NFE exome

AF:

0.265

Gnomad4 OTH exome

AF:

0.257

GnomAD4 genome

AF:

0.220

AC:

33540

AN:

152150

Hom.:

3975

Cov.:

AF XY:

0.218

AC XY:

16219

AN XY:

74372

show subpopulations

Gnomad4 AFR

AF:

0.126

Gnomad4 AMR

AF:

0.220

Gnomad4 ASJ

AF:

0.301

Gnomad4 EAS

AF:

0.333

Gnomad4 SAS

AF:

0.227

Gnomad4 FIN

AF:

0.217

Gnomad4 NFE

AF:

0.264

Gnomad4 OTH

AF:

0.250

Alfa

AF:

0.248

Hom.:

3822

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

DANN

Benign

0.34

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over