rs12468225

Variant names:

• chr2-24699490-C-A
• rs12468225
• NM_003743.5:c.949+1692C>A

Your query was ambiguous. Multiple possible variants found:

• chr2-24699490-C-A
• chr2-24699490-C-G
• chr2-24699490-C-T

Variant summary

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

The NM_003743.5(NCOA1):​c.949+1692C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.751 in 151,960 control chromosomes in the GnomAD database, including 44,751 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 0.75 (44751 hom., cov: 31)
• Consequence: NCOA1 NM_003743.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.629
• Publications: 4 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=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.848 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NCOA1	NM_003743.5	c.949+1692C>A		intron_variant	Intron 11 of 22	ENST00000348332.8	NP_003734.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NCOA1	ENST00000348332.8	c.949+1692C>A		intron_variant	Intron 11 of 22	1	NM_003743.5	ENSP00000320940.5

Frequencies

GnomAD3 genomes AF: 0.751 AC: 114105 AN: 151842 Hom.: 44730 Cov.: 31

Gnomad AFR AF: 0.503

Gnomad AMI AF: 0.864

Gnomad AMR AF: 0.853

Gnomad ASJ AF: 0.856

Gnomad EAS AF: 0.799

Gnomad SAS AF: 0.773

Gnomad FIN AF: 0.833

Gnomad MID AF: 0.807

Gnomad NFE AF: 0.853

Gnomad OTH AF: 0.783

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

GnomAD4 genome AF: 0.751 AC: 114166 AN: 151960 Hom.: 44751 Cov.: 31 AF XY: 0.753 AC XY: 55880 AN XY: 74256

African (AFR) AF: 0.503 AC: 20815 AN: 41370

American (AMR) AF: 0.853 AC: 13051 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.856 AC: 2966 AN: 3466

East Asian (EAS) AF: 0.798 AC: 4125 AN: 5168

South Asian (SAS) AF: 0.772 AC: 3718 AN: 4818

European-Finnish (FIN) AF: 0.833 AC: 8782 AN: 10546

Middle Eastern (MID) AF: 0.806 AC: 237 AN: 294

European-Non Finnish (NFE) AF: 0.854 AC: 58026 AN: 67984

Other (OTH) AF: 0.787 AC: 1658 AN: 2108

Alfa AF: 0.787 Hom.: 6252

Bravo AF: 0.742

Asia WGS AF: 0.800 AC: 2778 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.26
DANN	Benign	0.41
PhyloP100		-0.63
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: rs12468225; hg19: chr2-24922359;