chr2-24755628-G-A

Variant names:

• chr2-24755628-G-A
• rs12617941
• NM_003743.5:c.3882-2345G>A

Variant summary

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

The NM_003743.5(NCOA1):​c.3882-2345G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0744 in 152,252 control chromosomes in the GnomAD database, including 516 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 0.074 (516 hom., cov: 32)
• Consequence: NCOA1 NM_003743.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.703
• 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.116 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NCOA1	NM_003743.5	c.3882-2345G>A		intron_variant	Intron 20 of 22	ENST00000348332.8	NP_003734.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NCOA1	ENST00000348332.8	c.3882-2345G>A		intron_variant	Intron 20 of 22	1	NM_003743.5	ENSP00000320940.5

Frequencies

GnomAD3 genomes AF: 0.0744 AC: 11318 AN: 152136 Hom.: 517 Cov.: 32

Gnomad AFR AF: 0.119

Gnomad AMI AF: 0.131

Gnomad AMR AF: 0.0730

Gnomad ASJ AF: 0.0320

Gnomad EAS AF: 0.106

Gnomad SAS AF: 0.0912

Gnomad FIN AF: 0.0626

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0474

Gnomad OTH AF: 0.0708

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

GnomAD4 genome AF: 0.0744 AC: 11332 AN: 152252 Hom.: 516 Cov.: 32 AF XY: 0.0765 AC XY: 5698 AN XY: 74442

African (AFR) AF: 0.119 AC: 4946 AN: 41522

American (AMR) AF: 0.0728 AC: 1114 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0320 AC: 111 AN: 3472

East Asian (EAS) AF: 0.106 AC: 548 AN: 5182

South Asian (SAS) AF: 0.0922 AC: 444 AN: 4818

European-Finnish (FIN) AF: 0.0626 AC: 664 AN: 10610

Middle Eastern (MID) AF: 0.0476 AC: 14 AN: 294

European-Non Finnish (NFE) AF: 0.0474 AC: 3226 AN: 68030

Other (OTH) AF: 0.0691 AC: 146 AN: 2112

Alfa AF: 0.0565 Hom.: 144

Bravo AF: 0.0771

Asia WGS AF: 0.108 AC: 378 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.0
DANN	Benign	0.47
PhyloP100		0.70
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: rs12617941; hg19: chr2-24978497;