rs17737058

Variant names:

• chr2-24768700-C-G
• rs17737058
• NM_003743.5:c.*309C>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 15 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003743.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NCOA1	NM_003743.5	MANE Select	c.*309C>G		3_prime_UTR	Exon 23 of 23	NP_003734.3
	NCOA1	NM_147233.2		c.*309C>G		3_prime_UTR	Exon 21 of 21	NP_671766.1
	NCOA1	NM_001362950.1		c.*492C>G		3_prime_UTR	Exon 24 of 24	NP_001349879.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NCOA1	ENST00000348332.8	TSL:1 MANE Select	c.*309C>G		3_prime_UTR	Exon 23 of 23	ENSP00000320940.5
	NCOA1	ENST00000395856.3	TSL:1	c.*309C>G		3_prime_UTR	Exon 21 of 21	ENSP00000379197.3
	NCOA1	ENST00000288599.9	TSL:1	c.*492C>G		3_prime_UTR	Exon 22 of 22	ENSP00000288599.5

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

African (AFR) AF: 0.114 AC: 401 AN: 3510

American (AMR) AF: 0.0902 AC: 244 AN: 2706

Ashkenazi Jewish (ASJ) AF: 0.229 AC: 1077 AN: 4700

East Asian (EAS) AF: 0.104 AC: 1094 AN: 10540

South Asian (SAS) AF: 0.0956 AC: 112 AN: 1172

European-Finnish (FIN) AF: 0.255 AC: 163 AN: 638

Middle Eastern (MID) AF: 0.156 AC: 68 AN: 436

European-Non Finnish (NFE) AF: 0.202 AC: 9957 AN: 49208

Other (OTH) AF: 0.187 AC: 1192 AN: 6384

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

African (AFR) AF: 0.116 AC: 4828 AN: 41490

American (AMR) AF: 0.124 AC: 1900 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.241 AC: 838 AN: 3470

East Asian (EAS) AF: 0.122 AC: 631 AN: 5166

South Asian (SAS) AF: 0.103 AC: 496 AN: 4824

European-Finnish (FIN) AF: 0.262 AC: 2762 AN: 10556

Middle Eastern (MID) AF: 0.167 AC: 49 AN: 294

European-Non Finnish (NFE) AF: 0.223 AC: 15167 AN: 67984

Other (OTH) AF: 0.165 AC: 348 AN: 2104

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
CADD	Benign	15
DANN	Benign	0.83
PhyloP100		1.5
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: rs17737058; hg19: chr2-24991569;