rs17046513

Positions:

• chr2-24741626-A-C
• chr2-24741626-A-T

Variant summary

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

The NM_003743.5(NCOA1):​c.3304-158A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0461 in 152,288 control chromosomes in the GnomAD database, including 257 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 0.046 (257 hom., cov: 32)
• Consequence: NCOA1 NM_003743.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0670

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=-0.75).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.181 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NCOA1	NM_003743.5	c.3304-158A>C		intron_variant		ENST00000348332.8	NP_003734.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NCOA1	ENST00000348332.8	c.3304-158A>C		intron_variant		1	NM_003743.5	ENSP00000320940

Frequencies

GnomAD3 genomes AF: 0.0460 AC: 7002 AN: 152168 Hom.: 250 Cov.: 32

Gnomad AFR AF: 0.0254

Gnomad AMI AF: 0.0395

Gnomad AMR AF: 0.0407

Gnomad ASJ AF: 0.0346

Gnomad EAS AF: 0.190

Gnomad SAS AF: 0.0573

Gnomad FIN AF: 0.0664

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0454

Gnomad OTH AF: 0.0435

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

GnomAD4 genome AF: 0.0461 AC: 7017 AN: 152288 Hom.: 257 Cov.: 32 AF XY: 0.0482 AC XY: 3586 AN XY: 74456

Gnomad4 AFR AF: 0.0257

Gnomad4 AMR AF: 0.0407

Gnomad4 ASJ AF: 0.0346

Gnomad4 EAS AF: 0.191

Gnomad4 SAS AF: 0.0576

Gnomad4 FIN AF: 0.0664

Gnomad4 NFE AF: 0.0454

Gnomad4 OTH AF: 0.0426

Alfa AF: 0.0444 Hom.: 52

Bravo AF: 0.0454

Asia WGS AF: 0.0890 AC: 311 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	4.1
DANN	Benign	0.80

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: rs17046513; hg19: chr2-24964495;