Genetic Variant NCOA4:c.*351C>G (chr10-46006241-G-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_001145263.2(NCOA4):c.*351C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0578 in 327,474 control chromosomes in the GnomAD database, including 620 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 0.053 ( 247 hom., cov: 32)

Exomes 𝑓: 0.062 ( 373 hom. )

Consequence

NCOA4
NM_001145263.2 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.00500

Publications

9 publications found

Variant links:

Genes affected

NCOA4 (HGNC:7671): (nuclear receptor coactivator 4) This gene encodes an androgen receptor coactivator. The encoded protein interacts with the androgen receptor in a ligand-dependent manner to enhance its transcriptional activity. Chromosomal translocations between this gene and the ret tyrosine kinase gene, also located on chromosome 10, have been associated with papillary thyroid carcinoma. Alternatively spliced transcript variants have been described. Pseudogenes are present on chromosomes 4, 5, 10, and 14. [provided by RefSeq, Feb 2009]

NCOA4 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=-0.8).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0741 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NCOA4	NM_001145263.2 link	c.*351C>G		3_prime_UTR_variant	Exon 10 of 10	ENST00000581486.6	NP_001138735.1	Q13772-1A0A024QZI5B2R5V0Q96E88

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NCOA4	ENST00000581486.6 link	c.*351C>G		3_prime_UTR_variant	Exon 10 of 10	1	NM_001145263.2	ENSP00000462943.1		Q13772-1

Frequencies

GnomAD3 genomes

AF:

0.0526

AC:

8007

AN:

152098

Hom.:

247

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0161

Gnomad AMI

AF:

0.128

Gnomad AMR

AF:

0.0507

Gnomad ASJ

AF:

0.0594

Gnomad EAS

AF:

0.0227

Gnomad SAS

AF:

0.0497

Gnomad FIN

AF:

0.0558

Gnomad MID

AF:

0.0696

Gnomad NFE

AF:

0.0758

Gnomad OTH

AF:

0.0574

GnomAD4 exome

AF:

0.0623

AC:

10916

AN:

175258

Hom.:

373

Cov.:

AF XY:

0.0611

AC XY:

5355

AN XY:

87692

show subpopulations

African (AFR)

AF:

0.0131

AC:

101

AN:

7728

American (AMR)

AF:

0.0432

AC:

335

AN:

7752

Ashkenazi Jewish (ASJ)

AF:

0.0605

AC:

444

AN:

7336

East Asian (EAS)

AF:

0.0268

AC:

478

AN:

17804

South Asian (SAS)

AF:

0.0486

AC:

456

AN:

9390

European-Finnish (FIN)

AF:

0.0571

AC:

366

AN:

6406

Middle Eastern (MID)

AF:

0.0486

AC:

AN:

864

European-Non Finnish (NFE)

AF:

0.0753

AC:

7987

AN:

106014

Other (OTH)

AF:

0.0591

AC:

707

AN:

11964

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

521

1042

1562

2083

2604

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

138

184

230

<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:

0.0526

AC:

8004

AN:

152216

Hom.:

247

Cov.:

AF XY:

0.0511

AC XY:

3806

AN XY:

74418

show subpopulations

African (AFR)

AF:

0.0160

AC:

666

AN:

41544

American (AMR)

AF:

0.0507

AC:

774

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.0594

AC:

206

AN:

3470

East Asian (EAS)

AF:

0.0228

AC:

118

AN:

5186

South Asian (SAS)

AF:

0.0496

AC:

239

AN:

4822

European-Finnish (FIN)

AF:

0.0558

AC:

591

AN:

10586

Middle Eastern (MID)

AF:

0.0680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0758

AC:

5154

AN:

68008

Other (OTH)

AF:

0.0563

AC:

119

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

386

772

1159

1545

1931

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

196

294

392

490

<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:

0.0287

Hom.:

Bravo

AF:

0.0500

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

1.0

(source)

DANN

Benign

0.56

PhyloP100

0.0050

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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