rs6720514

chr2-24603750-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003743.5(NCOA1):c.-175+19190T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.193 in 152,148 control chromosomes in the GnomAD database, including 2,986 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 (2986 hom., cov: 32)
• Consequence: NCOA1 NM_003743.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.516

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.226 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NCOA1	NM_003743.5	c.-175+19190T>C		intron_variant		ENST00000348332.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NCOA1	ENST00000348332.8	c.-175+19190T>C		intron_variant		1	NM_003743.5

Frequencies

GnomAD3 genomes AF: 0.193 AC: 29269 AN: 152030 Hom.: 2983 Cov.: 32

Gnomad AFR AF: 0.152

Gnomad AMI AF: 0.392

Gnomad AMR AF: 0.130

Gnomad ASJ AF: 0.179

Gnomad EAS AF: 0.116

Gnomad SAS AF: 0.155

Gnomad FIN AF: 0.257

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.229

Gnomad OTH AF: 0.174

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

GnomAD4 genome AF: 0.193 AC: 29299 AN: 152148 Hom.: 2986 Cov.: 32 AF XY: 0.193 AC XY: 14324 AN XY: 74404

Gnomad4 AFR AF: 0.152

Gnomad4 AMR AF: 0.130

Gnomad4 ASJ AF: 0.179

Gnomad4 EAS AF: 0.116

Gnomad4 SAS AF: 0.155

Gnomad4 FIN AF: 0.257

Gnomad4 NFE AF: 0.229

Gnomad4 OTH AF: 0.173

Alfa AF: 0.220 Hom.: 1723

Bravo AF: 0.181

Asia WGS AF: 0.122 AC: 423 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	2.4
Dann	Benign	0.58

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

Publications

LitVar

Other links and lift over

dbSNP: rs6720514; hg19: chr2-24826619;