rs17791703

Variant names:

• chr2-24658402-T-C
• rs17791703
• NM_003743.5:c.-17-259T>C

Variant summary

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

The NM_003743.5(NCOA1):​c.-17-259T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.154 in 152,238 control chromosomes in the GnomAD database, including 2,171 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 0.15 (2171 hom., cov: 32)
• Consequence: NCOA1 NM_003743.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0900
• Publications: 7 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=-0.75).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.205 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NCOA1	NM_003743.5	c.-17-259T>C		intron_variant	Intron 4 of 22	ENST00000348332.8	NP_003734.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NCOA1	ENST00000348332.8	c.-17-259T>C		intron_variant	Intron 4 of 22	1	NM_003743.5	ENSP00000320940.5

Frequencies

GnomAD3 genomes AF: 0.154 AC: 23463 AN: 152120 Hom.: 2171 Cov.: 32

Gnomad AFR AF: 0.0629

Gnomad AMI AF: 0.284

Gnomad AMR AF: 0.109

Gnomad ASJ AF: 0.188

Gnomad EAS AF: 0.118

Gnomad SAS AF: 0.123

Gnomad FIN AF: 0.243

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.208

Gnomad OTH AF: 0.142

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.154 AC: 23473 AN: 152238 Hom.: 2171 Cov.: 32 AF XY: 0.155 AC XY: 11520 AN XY: 74428

African (AFR) AF: 0.0630 AC: 2617 AN: 41562

American (AMR) AF: 0.109 AC: 1671 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.188 AC: 654 AN: 3470

East Asian (EAS) AF: 0.118 AC: 611 AN: 5184

South Asian (SAS) AF: 0.123 AC: 595 AN: 4826

European-Finnish (FIN) AF: 0.243 AC: 2580 AN: 10596

Middle Eastern (MID) AF: 0.194 AC: 57 AN: 294

European-Non Finnish (NFE) AF: 0.208 AC: 14130 AN: 67984

Other (OTH) AF: 0.142 AC: 300 AN: 2116

Alfa AF: 0.181 Hom.: 693

Bravo AF: 0.140

Asia WGS AF: 0.105 AC: 364 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	5.6
DANN	Benign	0.88
PhyloP100		0.090
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: rs17791703; hg19: chr2-24881271;