chr2-24501916-T-G

Position:

• chr2-24501916-T-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The ENST00000348332.8(NCOA1):​c.-396+10314T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.463 in 152,020 control chromosomes in the GnomAD database, including 19,384 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 0.46 (19384 hom., cov: 31)
• Consequence: NCOA1 ENST00000348332.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0460

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.35).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.725 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NCOA1	NM_003743.5	c.-396+10314T>G		intron_variant		ENST00000348332.8	NP_003734.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NCOA1	ENST00000348332.8	c.-396+10314T>G		intron_variant		1	NM_003743.5	ENSP00000320940

Frequencies

GnomAD3 genomes AF: 0.463 AC: 70385 AN: 151902 Hom.: 19369 Cov.: 31

Gnomad AFR AF: 0.157

Gnomad AMI AF: 0.471

Gnomad AMR AF: 0.638

Gnomad ASJ AF: 0.596

Gnomad EAS AF: 0.745

Gnomad SAS AF: 0.609

Gnomad FIN AF: 0.522

Gnomad MID AF: 0.601

Gnomad NFE AF: 0.561

Gnomad OTH AF: 0.502

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

GnomAD4 genome AF: 0.463 AC: 70404 AN: 152020 Hom.: 19384 Cov.: 31 AF XY: 0.469 AC XY: 34813 AN XY: 74302

Gnomad4 AFR AF: 0.156

Gnomad4 AMR AF: 0.639

Gnomad4 ASJ AF: 0.596

Gnomad4 EAS AF: 0.745

Gnomad4 SAS AF: 0.607

Gnomad4 FIN AF: 0.522

Gnomad4 NFE AF: 0.561

Gnomad4 OTH AF: 0.508

Alfa AF: 0.553 Hom.: 38359

Bravo AF: 0.459

Asia WGS AF: 0.652 AC: 2267 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.35
CADD	Benign	5.0
DANN	Benign	0.80

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: rs1822300; hg19: chr2-24724785;