Variant chr2-24752089-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_003743.5(NCOA1):c.3814C>T(p.Pro1272Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0217 in 1,614,086 control chromosomes in the GnomAD database, including 452 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.016 ( 29 hom., cov: 32)

Exomes 𝑓: 0.022 ( 423 hom. )

Consequence

NCOA1
NM_003743.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.88

Variant links:

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]

NCOA1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0031810105).

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.016 (2430/152292) while in subpopulation NFE AF= 0.0259 (1760/68014). AF 95% confidence interval is 0.0249. There are 29 homozygotes in gnomad4. There are 1121 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 2430 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NCOA1	NM_003743.5 linkuse as main transcript	c.3814C>T	p.Pro1272Ser	missense_variant	20/23	ENST00000348332.8	NP_003734.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NCOA1	ENST00000348332.8 linkuse as main transcript	c.3814C>T	p.Pro1272Ser	missense_variant	20/23	1	NM_003743.5	ENSP00000320940		Q15788-1

Frequencies

GnomAD3 genomes

AF:

0.0160

AC:

2431

AN:

152174

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00487

Gnomad AMI

AF:

0.0296

Gnomad AMR

AF:

0.0166

Gnomad ASJ

AF:

0.0115

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00932

Gnomad FIN

AF:

0.00556

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.0259

Gnomad OTH

AF:

0.0181

GnomAD3 exomes

AF:

0.0169

AC:

4245

AN:

251356

Hom.:

AF XY:

0.0177

AC XY:

2410

AN XY:

135842

show subpopulations

Gnomad AFR exome

AF:

0.00357

Gnomad AMR exome

AF:

0.0136

Gnomad ASJ exome

AF:

0.0129

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.0120

Gnomad FIN exome

AF:

0.00582

Gnomad NFE exome

AF:

0.0262

Gnomad OTH exome

AF:

0.0176

GnomAD4 exome

AF:

0.0223

AC:

32665

AN:

1461794

Hom.:

423

Cov.:

AF XY:

0.0223

AC XY:

16244

AN XY:

727188

show subpopulations

Gnomad4 AFR exome

AF:

0.00376

Gnomad4 AMR exome

AF:

0.0145

Gnomad4 ASJ exome

AF:

0.0114

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0123

Gnomad4 FIN exome

AF:

0.00681

Gnomad4 NFE exome

AF:

0.0259

Gnomad4 OTH exome

AF:

0.0206

GnomAD4 genome

AF:

0.0160

AC:

2430

AN:

152292

Hom.:

Cov.:

AF XY:

0.0151

AC XY:

1121

AN XY:

74474

show subpopulations

Gnomad4 AFR

AF:

0.00486

Gnomad4 AMR

AF:

0.0166

Gnomad4 ASJ

AF:

0.0115

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00912

Gnomad4 FIN

AF:

0.00556

Gnomad4 NFE

AF:

0.0259

Gnomad4 OTH

AF:

0.0175

Alfa

AF:

0.0237

Hom.:

Bravo

AF:

0.0170

TwinsUK

AF:

0.0245

AC:

ALSPAC

AF:

0.0298

AC:

115

ESP6500AA

AF:

0.00704

AC:

ESP6500EA

AF:

0.0293

AC:

252

ExAC

AF:

0.0168

AC:

2045

Asia WGS

AF:

0.00491

AC:

AN:

3478

EpiCase

AF:

0.0276

EpiControl

AF:

0.0288

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.058

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.58

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.15

T;.;T;.;T;.

Eigen

Benign

0.029

Eigen_PC

Benign

0.18

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.93

.;.;D;D;D;D

MetaRNN

Benign

0.0032

T;T;T;T;T;T

MetaSVM

Benign

-0.76

MutationAssessor

Benign

1.6

L;L;.;L;L;L

MutationTaster

Benign

1.0

D;D;D;D;D;D;D

PrimateAI

Benign

0.45

PROVEAN

Benign

-1.1

N;N;N;N;N;N

REVEL

Benign

0.11

Sift

Uncertain

0.014

D;D;D;D;D;D

Sift4G

Benign

0.49

T;T;T;T;T;T

Polyphen

0.19

B;B;B;B;B;B

Vest4

0.16

MPC

0.28

ClinPred

0.013

GERP RS

5.1

Varity_R

0.12

gMVP

0.20

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