2-24661808-A-G

Variant names:

• chr2-24661808-A-G
• rs6746301
• NM_003743.5:c.89+3042A>G

Variant summary

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

The NM_003743.5(NCOA1):​c.89+3042A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.079 in 152,124 control chromosomes in the GnomAD database, including 552 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 0.079 (552 hom., cov: 32)
• Consequence: NCOA1 NM_003743.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.727
• Publications: 3 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=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.117 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.89+3042A>G		intron	N/A	NP_003734.3
	NCOA1	NM_147233.2		c.89+3042A>G		intron	N/A	NP_671766.1
	NCOA1	NM_001362950.1		c.89+3042A>G		intron	N/A	NP_001349879.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NCOA1	ENST00000348332.8	TSL:1 MANE Select	c.89+3042A>G		intron	N/A	ENSP00000320940.5
	NCOA1	ENST00000395856.3	TSL:1	c.89+3042A>G		intron	N/A	ENSP00000379197.3
	NCOA1	ENST00000288599.9	TSL:1	c.89+3042A>G		intron	N/A	ENSP00000288599.5

Frequencies

GnomAD3 genomes AF: 0.0789 AC: 12000 AN: 152006 Hom.: 553 Cov.: 32

Gnomad AFR AF: 0.118

Gnomad AMI AF: 0.148

Gnomad AMR AF: 0.0756

Gnomad ASJ AF: 0.0369

Gnomad EAS AF: 0.126

Gnomad SAS AF: 0.0984

Gnomad FIN AF: 0.0698

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0538

Gnomad OTH AF: 0.0755

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

GnomAD4 genome AF: 0.0790 AC: 12015 AN: 152124 Hom.: 552 Cov.: 32 AF XY: 0.0814 AC XY: 6051 AN XY: 74368

African (AFR) AF: 0.118 AC: 4909 AN: 41492

American (AMR) AF: 0.0754 AC: 1152 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0369 AC: 128 AN: 3470

East Asian (EAS) AF: 0.125 AC: 647 AN: 5172

South Asian (SAS) AF: 0.0993 AC: 478 AN: 4812

European-Finnish (FIN) AF: 0.0698 AC: 737 AN: 10566

Middle Eastern (MID) AF: 0.0544 AC: 16 AN: 294

European-Non Finnish (NFE) AF: 0.0538 AC: 3657 AN: 68006

Other (OTH) AF: 0.0738 AC: 156 AN: 2114

Alfa AF: 0.0686 Hom.: 56

Bravo AF: 0.0814

Asia WGS AF: 0.117 AC: 407 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.31
DANN	Benign	0.34
PhyloP100		-0.73
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs6746301; hg19: chr2-24884677;