chr2-24724181-G-T

Variant names:

• chr2-24724181-G-T
• rs11682130
• NM_003743.5:c.2600-2408G>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.2600-2408G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.489 in 151,858 control chromosomes in the GnomAD database, including 19,795 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 0.49 (19795 hom., cov: 31)
• Consequence: NCOA1 NM_003743.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.215
• Publications: 5 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.634 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NCOA1	NM_003743.5	c.2600-2408G>T		intron_variant	Intron 14 of 22	ENST00000348332.8	NP_003734.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NCOA1	ENST00000348332.8	c.2600-2408G>T		intron_variant	Intron 14 of 22	1	NM_003743.5	ENSP00000320940.5

Frequencies

GnomAD3 genomes AF: 0.489 AC: 74172 AN: 151740 Hom.: 19782 Cov.: 31

Gnomad AFR AF: 0.259

Gnomad AMI AF: 0.424

Gnomad AMR AF: 0.644

Gnomad ASJ AF: 0.549

Gnomad EAS AF: 0.576

Gnomad SAS AF: 0.547

Gnomad FIN AF: 0.523

Gnomad MID AF: 0.551

Gnomad NFE AF: 0.574

Gnomad OTH AF: 0.533

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

GnomAD4 genome AF: 0.489 AC: 74203 AN: 151858 Hom.: 19795 Cov.: 31 AF XY: 0.490 AC XY: 36328 AN XY: 74208

African (AFR) AF: 0.259 AC: 10736 AN: 41424

American (AMR) AF: 0.644 AC: 9827 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.549 AC: 1904 AN: 3468

East Asian (EAS) AF: 0.575 AC: 2974 AN: 5168

South Asian (SAS) AF: 0.544 AC: 2627 AN: 4826

European-Finnish (FIN) AF: 0.523 AC: 5501 AN: 10514

Middle Eastern (MID) AF: 0.548 AC: 160 AN: 292

European-Non Finnish (NFE) AF: 0.574 AC: 38954 AN: 67906

Other (OTH) AF: 0.539 AC: 1136 AN: 2106

Alfa AF: 0.545 Hom.: 18540

Bravo AF: 0.487

Asia WGS AF: 0.579 AC: 2011 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	8.2
DANN	Benign	0.77
PhyloP100		-0.21
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: rs11682130; hg19: chr2-24947050;