rs4578807

Positions:

• chr2-24699566-G-A
• chr2-24699566-G-T

Variant summary

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

The ENST00000348332.8(NCOA1):​c.949+1768G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.764 in 151,594 control chromosomes in the GnomAD database, including 45,757 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 0.76 (45757 hom., cov: 29)
• Consequence: NCOA1 ENST00000348332.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.191

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=-1.01).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.85 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NCOA1	NM_003743.5	c.949+1768G>A		intron_variant		ENST00000348332.8	NP_003734.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NCOA1	ENST00000348332.8	c.949+1768G>A		intron_variant		1	NM_003743.5	ENSP00000320940

Frequencies

GnomAD3 genomes AF: 0.764 AC: 115688 AN: 151478 Hom.: 45733 Cov.: 29

Gnomad AFR AF: 0.536

Gnomad AMI AF: 0.865

Gnomad AMR AF: 0.861

Gnomad ASJ AF: 0.856

Gnomad EAS AF: 0.798

Gnomad SAS AF: 0.775

Gnomad FIN AF: 0.850

Gnomad MID AF: 0.813

Gnomad NFE AF: 0.856

Gnomad OTH AF: 0.793

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

GnomAD4 genome AF: 0.764 AC: 115753 AN: 151594 Hom.: 45757 Cov.: 29 AF XY: 0.765 AC XY: 56679 AN XY: 74068

Gnomad4 AFR AF: 0.536

Gnomad4 AMR AF: 0.861

Gnomad4 ASJ AF: 0.856

Gnomad4 EAS AF: 0.797

Gnomad4 SAS AF: 0.773

Gnomad4 FIN AF: 0.850

Gnomad4 NFE AF: 0.856

Gnomad4 OTH AF: 0.796

Alfa AF: 0.829 Hom.: 20524

Bravo AF: 0.755

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.082
DANN	Benign	0.69

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: rs4578807; hg19: chr2-24922435;