rs2044148

Variant names:

• chr2-24514964-G-A
• rs2044148
• NM_003743.5:c.-396+23362G>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.-396+23362G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.148 in 152,036 control chromosomes in the GnomAD database, including 2,026 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 0.15 (2026 hom., cov: 31)
• Consequence: NCOA1 NM_003743.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.605
• 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.201 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NCOA1	NM_003743.5	c.-396+23362G>A		intron_variant	Intron 1 of 22	ENST00000348332.8	NP_003734.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NCOA1	ENST00000348332.8	c.-396+23362G>A		intron_variant	Intron 1 of 22	1	NM_003743.5	ENSP00000320940.5

Frequencies

GnomAD3 genomes AF: 0.148 AC: 22545 AN: 151920 Hom.: 2026 Cov.: 31

Gnomad AFR AF: 0.0582

Gnomad AMI AF: 0.282

Gnomad AMR AF: 0.102

Gnomad ASJ AF: 0.159

Gnomad EAS AF: 0.114

Gnomad SAS AF: 0.103

Gnomad FIN AF: 0.236

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.204

Gnomad OTH AF: 0.137

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

GnomAD4 genome AF: 0.148 AC: 22558 AN: 152036 Hom.: 2026 Cov.: 31 AF XY: 0.148 AC XY: 11020 AN XY: 74310

African (AFR) AF: 0.0584 AC: 2422 AN: 41496

American (AMR) AF: 0.102 AC: 1564 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.159 AC: 553 AN: 3470

East Asian (EAS) AF: 0.114 AC: 591 AN: 5172

South Asian (SAS) AF: 0.104 AC: 498 AN: 4810

European-Finnish (FIN) AF: 0.236 AC: 2488 AN: 10542

Middle Eastern (MID) AF: 0.156 AC: 46 AN: 294

European-Non Finnish (NFE) AF: 0.204 AC: 13852 AN: 67956

Other (OTH) AF: 0.136 AC: 288 AN: 2112

Alfa AF: 0.190 Hom.: 1869

Bravo AF: 0.135

Asia WGS AF: 0.0940 AC: 327 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.5
DANN	Benign	0.78
PhyloP100		-0.60
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: rs2044148; hg19: chr2-24737833;