2-24721103-A-G

Variant names:

• chr2-24721103-A-G
• rs4665716
• NM_003743.5:c.2600-5486A>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.2600-5486A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0824 in 152,218 control chromosomes in the GnomAD database, including 574 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 0.082 (574 hom., cov: 32)
• Consequence: NCOA1 NM_003743.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.160
• Publications: 10 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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.117 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NCOA1	NM_003743.5	c.2600-5486A>G		intron_variant	Intron 14 of 22	ENST00000348332.8	NP_003734.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NCOA1	ENST00000348332.8	c.2600-5486A>G		intron_variant	Intron 14 of 22	1	NM_003743.5	ENSP00000320940.5

Frequencies

GnomAD3 genomes AF: 0.0824 AC: 12527 AN: 152100 Hom.: 576 Cov.: 32

Gnomad AFR AF: 0.120

Gnomad AMI AF: 0.174

Gnomad AMR AF: 0.0773

Gnomad ASJ AF: 0.0482

Gnomad EAS AF: 0.107

Gnomad SAS AF: 0.101

Gnomad FIN AF: 0.0652

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.0610

Gnomad OTH AF: 0.0785

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

GnomAD4 genome AF: 0.0824 AC: 12543 AN: 152218 Hom.: 574 Cov.: 32 AF XY: 0.0840 AC XY: 6252 AN XY: 74426

African (AFR) AF: 0.120 AC: 4979 AN: 41536

American (AMR) AF: 0.0771 AC: 1179 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0482 AC: 167 AN: 3468

East Asian (EAS) AF: 0.107 AC: 554 AN: 5190

South Asian (SAS) AF: 0.101 AC: 488 AN: 4814

European-Finnish (FIN) AF: 0.0652 AC: 690 AN: 10584

Middle Eastern (MID) AF: 0.0646 AC: 19 AN: 294

European-Non Finnish (NFE) AF: 0.0610 AC: 4146 AN: 68014

Other (OTH) AF: 0.0767 AC: 162 AN: 2112

Alfa AF: 0.0620 Hom.: 226

Bravo AF: 0.0850

Asia WGS AF: 0.115 AC: 401 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.1
DANN	Benign	0.71
PhyloP100		0.16
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: rs4665716; hg19: chr2-24943972;