rs17737058

Positions:

• chr2-24768700-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003743.5(NCOA1):​c.*309C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.18 in 231,386 control chromosomes in the GnomAD database, including 4,172 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 0.18 (2701 hom., cov: 32)
  • Exomes 𝑓: 0.18 (1471 hom.)
• Consequence: NCOA1 NM_003743.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.54

Genes affected

NCOA1 (HGNC:7668): (nuclear receptor coactivator 1) The protein encoded by this gene acts as a transcriptional coactivator for steroid and nuclear hormone receptors. It is a member of the p160/steroid receptor coactivator (SRC) family and like other family members has histone acetyltransferase activity and contains a nuclear localization signal, as well as bHLH and PAS domains. The product of this gene binds nuclear receptors directly and stimulates the transcriptional activities in a hormone-dependent fashion. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.49).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.22 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NCOA1	NM_003743.5	c.*309C>G		3_prime_UTR_variant	23/23	ENST00000348332.8	NP_003734.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NCOA1	ENST00000348332.8	c.*309C>G		3_prime_UTR_variant	23/23	1	NM_003743.5	ENSP00000320940.5

Frequencies

GnomAD3 genomes AF: 0.179 AC: 27268 AN: 151974 Hom.: 2700 Cov.: 32

Gnomad AFR AF: 0.116

Gnomad AMI AF: 0.292

Gnomad AMR AF: 0.124

Gnomad ASJ AF: 0.241

Gnomad EAS AF: 0.122

Gnomad SAS AF: 0.103

Gnomad FIN AF: 0.262

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.223

Gnomad OTH AF: 0.166

GnomAD4 exome AF: 0.180 AC: 14308 AN: 79294 Hom.: 1471 Cov.: 0 AF XY: 0.181 AC XY: 6749 AN XY: 37362

Gnomad4 AFR exome AF: 0.114

Gnomad4 AMR exome AF: 0.0902

Gnomad4 ASJ exome AF: 0.229

Gnomad4 EAS exome AF: 0.104

Gnomad4 SAS exome AF: 0.0956

Gnomad4 FIN exome AF: 0.255

Gnomad4 NFE exome AF: 0.202

Gnomad4 OTH exome AF: 0.187

GnomAD4 genome AF: 0.179 AC: 27285 AN: 152092 Hom.: 2701 Cov.: 32 AF XY: 0.178 AC XY: 13253 AN XY: 74334

Gnomad4 AFR AF: 0.116

Gnomad4 AMR AF: 0.124

Gnomad4 ASJ AF: 0.241

Gnomad4 EAS AF: 0.122

Gnomad4 SAS AF: 0.103

Gnomad4 FIN AF: 0.262

Gnomad4 NFE AF: 0.223

Gnomad4 OTH AF: 0.165

Alfa AF: 0.207 Hom.: 441

Bravo AF: 0.168

Asia WGS AF: 0.104 AC: 361 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
CADD	Benign	15
DANN	Benign	0.83

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

Other links and lift over

dbSNP: rs17737058; hg19: chr2-24991569;