2-24746002-A-C

Variant names:

• chr2-24746002-A-C
• rs6743362
• NM_003743.5:c.3706+3816A>C

Variant summary

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

The NM_003743.5(NCOA1):​c.3706+3816A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0424 in 152,284 control chromosomes in the GnomAD database, including 214 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 0.042 (214 hom., cov: 31)
• Consequence: NCOA1 NM_003743.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.375
• 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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0908 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.3706+3816A>C		intron	N/A	NP_003734.3
	NCOA1	NM_147233.2		c.3706+3816A>C		intron	N/A	NP_671766.1
	NCOA1	NM_001362950.1		c.3706+3816A>C		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.3706+3816A>C		intron	N/A	ENSP00000320940.5
	NCOA1	ENST00000395856.3	TSL:1	c.3706+3816A>C		intron	N/A	ENSP00000379197.3
	NCOA1	ENST00000288599.9	TSL:1	c.3706+3816A>C		intron	N/A	ENSP00000288599.5

Frequencies

GnomAD3 genomes AF: 0.0423 AC: 6443 AN: 152166 Hom.: 213 Cov.: 31

Gnomad AFR AF: 0.0930

Gnomad AMI AF: 0.111

Gnomad AMR AF: 0.0238

Gnomad ASJ AF: 0.0112

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0313

Gnomad FIN AF: 0.0225

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0238

Gnomad OTH AF: 0.0320

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

GnomAD4 genome AF: 0.0424 AC: 6462 AN: 152284 Hom.: 214 Cov.: 31 AF XY: 0.0422 AC XY: 3143 AN XY: 74458

African (AFR) AF: 0.0933 AC: 3874 AN: 41542

American (AMR) AF: 0.0237 AC: 362 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0112 AC: 39 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5188

South Asian (SAS) AF: 0.0313 AC: 151 AN: 4824

European-Finnish (FIN) AF: 0.0225 AC: 239 AN: 10612

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.0238 AC: 1622 AN: 68024

Other (OTH) AF: 0.0317 AC: 67 AN: 2114

Alfa AF: 0.0315 Hom.: 53

Bravo AF: 0.0451

Asia WGS AF: 0.0200 AC: 70 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	5.6
DANN	Benign	0.35
PhyloP100		0.38
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: rs6743362; hg19: chr2-24968871;