chr2-24670190-A-T

Variant names:

• chr2-24670190-A-T
• rs7572475
• NM_003743.5:c.257-3176A>T

Variant summary

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

The NM_003743.5(NCOA1):​c.257-3176A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.19 in 152,104 control chromosomes in the GnomAD database, including 2,926 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 0.19 (2926 hom., cov: 32)
• Consequence: NCOA1 NM_003743.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.105
• 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 (NFE) allele frequency at 95% confidence interval = 0.225 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NCOA1	NM_003743.5	c.257-3176A>T		intron_variant	Intron 6 of 22	ENST00000348332.8	NP_003734.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NCOA1	ENST00000348332.8	c.257-3176A>T		intron_variant	Intron 6 of 22	1	NM_003743.5	ENSP00000320940.5

Frequencies

GnomAD3 genomes AF: 0.190 AC: 28812 AN: 151986 Hom.: 2923 Cov.: 32

Gnomad AFR AF: 0.148

Gnomad AMI AF: 0.395

Gnomad AMR AF: 0.127

Gnomad ASJ AF: 0.171

Gnomad EAS AF: 0.114

Gnomad SAS AF: 0.130

Gnomad FIN AF: 0.257

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.228

Gnomad OTH AF: 0.170

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

GnomAD4 genome AF: 0.190 AC: 28841 AN: 152104 Hom.: 2926 Cov.: 32 AF XY: 0.189 AC XY: 14048 AN XY: 74356

African (AFR) AF: 0.148 AC: 6141 AN: 41502

American (AMR) AF: 0.126 AC: 1934 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.171 AC: 593 AN: 3468

East Asian (EAS) AF: 0.114 AC: 589 AN: 5170

South Asian (SAS) AF: 0.130 AC: 629 AN: 4822

European-Finnish (FIN) AF: 0.257 AC: 2708 AN: 10550

Middle Eastern (MID) AF: 0.177 AC: 52 AN: 294

European-Non Finnish (NFE) AF: 0.228 AC: 15479 AN: 67982

Other (OTH) AF: 0.169 AC: 357 AN: 2114

Alfa AF: 0.214 Hom.: 521

Bravo AF: 0.179

Asia WGS AF: 0.112 AC: 389 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	2.9
DANN	Benign	0.34
PhyloP100		-0.10
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: rs7572475; hg19: chr2-24893059;