Variant rs3812430 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_006540.4(NCOA2):c.3158+66G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.169 in 1,532,942 control chromosomes in the GnomAD database, including 31,655 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 0.26 ( 7405 hom., cov: 33)

Exomes 𝑓: 0.16 ( 24250 hom. )

Consequence

NCOA2
NM_006540.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.344

Variant links:

Genes affected

NCOA2 (HGNC:7669): (nuclear receptor coactivator 2) The protein encoded by this gene functions as a transcriptional coactivator for nuclear hormone receptors, including steroid, thyroid, retinoid, and vitamin D receptors. The encoded protein acts as an intermediary factor for the ligand-dependent activity of these nuclear receptors, which regulate their target genes upon binding of cognate response elements. This gene has been found to be involved in translocations that result in fusions with other genes in various cancers, including the lysine acetyltransferase 6A (KAT6A) gene in acute myeloid leukemia, the ETS variant 6 (ETV6) gene in acute lymphoblastic leukemia, and the hes related family bHLH transcription factor with YRPW motif 1 (HEY1) gene in mesenchymal chondrosarcoma. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2016]

NCOA2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.96).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.511 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NCOA2	NM_006540.4 linkuse as main transcript	c.3158+66G>T		intron_variant		ENST00000452400.7	NP_006531.1

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	Appris
NCOA2	ENST00000452400.7 linkuse as main transcript	c.3158+66G>T	intron_variant		1	NM_006540.4	ENSP00000399968	P1
NCOA2	ENST00000518363.2 linkuse as main transcript	c.534+66G>T	intron_variant		2		ENSP00000429132
NCOA2	ENST00000522054.1 linkuse as main transcript	n.255G>T	non_coding_transcript_exon_variant	2/2	3
NCOA2	ENST00000518287.6 linkuse as main transcript	c.*115+66G>T	intron_variant, NMD_transcript_variant		5		ENSP00000430148

Frequencies

GnomAD3 genomes

AF:

0.257

AC:

39096

AN:

151972

Hom.:

7378

Cov.:

show subpopulations

Gnomad AFR

AF:

0.509

Gnomad AMI

AF:

0.0526

Gnomad AMR

AF:

0.171

Gnomad ASJ

AF:

0.188

Gnomad EAS

AF:

0.527

Gnomad SAS

AF:

0.329

Gnomad FIN

AF:

0.119

Gnomad MID

AF:

0.184

Gnomad NFE

AF:

0.127

Gnomad OTH

AF:

0.228

GnomAD4 exome

AF:

0.159

AC:

220052

AN:

1380852

Hom.:

24250

Cov.:

AF XY:

0.163

AC XY:

111660

AN XY:

686718

show subpopulations

Gnomad4 AFR exome

AF:

0.528

Gnomad4 AMR exome

AF:

0.142

Gnomad4 ASJ exome

AF:

0.181

Gnomad4 EAS exome

AF:

0.516

Gnomad4 SAS exome

AF:

0.309

Gnomad4 FIN exome

AF:

0.121

Gnomad4 NFE exome

AF:

0.125

Gnomad4 OTH exome

AF:

0.193

GnomAD4 genome

AF:

0.258

AC:

39172

AN:

152090

Hom.:

7405

Cov.:

AF XY:

0.258

AC XY:

19153

AN XY:

74362

show subpopulations

Gnomad4 AFR

AF:

0.509

Gnomad4 AMR

AF:

0.171

Gnomad4 ASJ

AF:

0.188

Gnomad4 EAS

AF:

0.528

Gnomad4 SAS

AF:

0.329

Gnomad4 FIN

AF:

0.119

Gnomad4 NFE

AF:

0.127

Gnomad4 OTH

AF:

0.230

Alfa

AF:

0.141

Hom.:

915

Bravo

AF:

0.269

Asia WGS

AF:

0.406

AC:

1407

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.96

CADD

Benign

0.21

DANN

Benign

0.46

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over