rs2903908

Variant names:

• chr20-46065308-T-C
• rs2903908
• NM_020967.3:c.630-80A>G

Your query was ambiguous. Multiple possible variants found:

• chr20-46065308-T-C
• chr20-46065308-T-G

Variant summary

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

The NM_020967.3(NCOA5):​c.630-80A>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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.471
• Publications: 13 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.32 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NCOA5	NM_020967.3	MANE Select	c.630-80A>G		intron	N/A	NP_066018.1	Q9HCD5
	NCOA5	NM_001348148.2		c.315-80A>G		intron	N/A	NP_001335077.1
	NCOA5	NM_001348149.2		c.630-80A>G		intron	N/A	NP_001335078.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NCOA5	ENST00000290231.11	TSL:1 MANE Select	c.630-80A>G		intron	N/A	ENSP00000290231.6	Q9HCD5
	NCOA5	ENST00000870777.1		c.630-80A>G		intron	N/A	ENSP00000540836.1
	NCOA5	ENST00000934594.1		c.630-80A>G		intron	N/A	ENSP00000604653.1

Frequencies

GnomAD3 genomes AF: 0.221 AC: 33544 AN: 152032 Hom.: 3978 Cov.: 32

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

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

GnomAD4 genome AF: 0.220 AC: 33540 AN: 152150 Hom.: 3975 Cov.: 32 AF XY: 0.218 AC XY: 16219 AN XY: 74372

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: 97 AN: 294

European-Non Finnish (NFE) AF: 0.264 AC: 17952 AN: 67980

Other (OTH) AF: 0.250 AC: 528 AN: 2112

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.43
DANN	Benign	0.34
PhyloP100		-0.47
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: rs2903908; hg19: chr20-44693947; COSMIC: COSV51643868; COSMIC: COSV51643868;