dbSNP rs6724282: NCOA1: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:

Genome browser will be placed here

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003743.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
NCOA1	NM_003743.5	MANE Select	c.*2412A>G	downstream_gene	N/A	NP_003734.3
NCOA1	NM_147233.2		c.*2412A>G	downstream_gene	N/A	NP_671766.1	Q15788-3
NCOA1	NM_001362950.1		c.*2595A>G	downstream_gene	N/A	NP_001349879.1	Q15788-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
NCOA1	ENST00000348332.8	TSL:1 MANE Select	c.*2412A>G	downstream_gene	N/A	ENSP00000320940.5	Q15788-1
NCOA1	ENST00000395856.3	TSL:1	c.*2412A>G	downstream_gene	N/A	ENSP00000379197.3	Q15788-3
NCOA1	ENST00000288599.9	TSL:1	c.*2595A>G	downstream_gene	N/A	ENSP00000288599.5	Q15788-2

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 v4.9

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over