2-24501916-T-G

Variant names:

• chr2-24501916-T-G
• rs1822300
• NM_003743.5:c.-396+10314T>G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_003743.5(NCOA1):​c.-396+10314T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.463 in 152,020 control chromosomes in the GnomAD database, including 19,384 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 0.46 (19384 hom., cov: 31)
• Consequence: NCOA1 NM_003743.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0460
• Publications: 8 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.35).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.725 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003743.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NCOA1	NM_003743.5	MANE Select	c.-396+10314T>G		intron	N/A	NP_003734.3
	NCOA1	NM_001362950.1		c.-396+10314T>G		intron	N/A	NP_001349879.1
	NCOA1	NM_001362952.1		c.-396+9728T>G		intron	N/A	NP_001349881.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NCOA1	ENST00000348332.8	TSL:1 MANE Select	c.-396+10314T>G		intron	N/A	ENSP00000320940.5
	NCOA1	ENST00000406961.5	TSL:5	c.-396+9728T>G		intron	N/A	ENSP00000385216.1
	NCOA1	ENST00000405141.5	TSL:5	c.-581+9728T>G		intron	N/A	ENSP00000385097.1

Frequencies

GnomAD3 genomes AF: 0.463 AC: 70385 AN: 151902 Hom.: 19369 Cov.: 31

Gnomad AFR AF: 0.157

Gnomad AMI AF: 0.471

Gnomad AMR AF: 0.638

Gnomad ASJ AF: 0.596

Gnomad EAS AF: 0.745

Gnomad SAS AF: 0.609

Gnomad FIN AF: 0.522

Gnomad MID AF: 0.601

Gnomad NFE AF: 0.561

Gnomad OTH AF: 0.502

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

GnomAD4 genome AF: 0.463 AC: 70404 AN: 152020 Hom.: 19384 Cov.: 31 AF XY: 0.469 AC XY: 34813 AN XY: 74302

African (AFR) AF: 0.156 AC: 6482 AN: 41462

American (AMR) AF: 0.639 AC: 9762 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.596 AC: 2066 AN: 3466

East Asian (EAS) AF: 0.745 AC: 3858 AN: 5180

South Asian (SAS) AF: 0.607 AC: 2929 AN: 4822

European-Finnish (FIN) AF: 0.522 AC: 5502 AN: 10550

Middle Eastern (MID) AF: 0.602 AC: 177 AN: 294

European-Non Finnish (NFE) AF: 0.561 AC: 38127 AN: 67942

Other (OTH) AF: 0.508 AC: 1073 AN: 2112

Alfa AF: 0.534 Hom.: 84911

Bravo AF: 0.459

Asia WGS AF: 0.652 AC: 2267 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.35
CADD	Benign	5.0
DANN	Benign	0.80
PhyloP100		0.046
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: rs1822300; hg19: chr2-24724785;