Genetic Variant NM_003743.5:c.*2412A>G (chr2-24770803-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_003743.5(NCOA1):c.*2412A>G variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0764 in 175,108 control chromosomes in the GnomAD database, including 636 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 0.075 ( 519 hom., cov: 32)

Exomes 𝑓: 0.087 ( 117 hom. )

Consequence

NCOA1
NM_003743.5 downstream_gene

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.581

Publications

12 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.117 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NCOA1	NM_003743.5 link	c.*2412A>G		downstream_gene_variant		ENST00000348332.8	NP_003734.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NCOA1	ENST00000348332.8 link	c.*2412A>G		downstream_gene_variant		1	NM_003743.5	ENSP00000320940.5		Q15788-1

Frequencies

GnomAD3 genomes

AF:

0.0748

AC:

11380

AN:

152190

Hom.:

520

Cov.:

show subpopulations

Gnomad AFR

AF:

0.119

Gnomad AMI

AF:

0.130

Gnomad AMR

AF:

0.0733

Gnomad ASJ

AF:

0.0320

Gnomad EAS

AF:

0.107

Gnomad SAS

AF:

0.0956

Gnomad FIN

AF:

0.0622

Gnomad MID

AF:

0.0506

Gnomad NFE

AF:

0.0477

Gnomad OTH

AF:

0.0708

GnomAD4 exome

AF:

0.0866

AC:

1975

AN:

22800

Hom.:

117

AF XY:

0.0886

AC XY:

925

AN XY:

10442

show subpopulations

African (AFR)

AF:

0.129

AC:

AN:

720

American (AMR)

AF:

0.0882

AC:

AN:

476

Ashkenazi Jewish (ASJ)

AF:

0.0385

AC:

AN:

1482

East Asian (EAS)

AF:

0.191

AC:

935

AN:

4904

South Asian (SAS)

AF:

0.0842

AC:

AN:

202

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AF:

0.0685

AC:

AN:

146

European-Non Finnish (NFE)

AF:

0.0546

AC:

712

AN:

13044

Other (OTH)

AF:

0.0601

AC:

109

AN:

1814

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

166

248

331

414

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0748

AC:

11397

AN:

152308

Hom.:

519

Cov.:

AF XY:

0.0770

AC XY:

5734

AN XY:

74478

show subpopulations

African (AFR)

AF:

0.120

AC:

4968

AN:

41560

American (AMR)

AF:

0.0730

AC:

1118

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.0320

AC:

111

AN:

3470

East Asian (EAS)

AF:

0.106

AC:

552

AN:

5190

South Asian (SAS)

AF:

0.0965

AC:

466

AN:

4828

European-Finnish (FIN)

AF:

0.0622

AC:

660

AN:

10618

Middle Eastern (MID)

AF:

0.0510

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0477

AC:

3242

AN:

68016

Other (OTH)

AF:

0.0691

AC:

146

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

534

1069

1603

2138

2672

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

134

268

402

536

670

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0549

Hom.:

217

Bravo

AF:

0.0775

Asia WGS

AF:

0.112

AC:

392

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

2.2

(source)

DANN

Benign

0.73

PhyloP100

0.58

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over