Genetic Variant NCOA4:p.Phe8Val (chr10-46027444-A-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000578454.5(NCOA4):c.22T>G(p.Phe8Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.434 in 1,549,152 control chromosomes in the GnomAD database, including 149,811 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 0.41 ( 13464 hom., cov: 32)

Exomes 𝑓: 0.44 ( 136347 hom. )

Consequence

NCOA4
ENST00000578454.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0220

Publications

51 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:

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 (MetaRNN=0.004737556).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.648 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NCOA4	NM_001145263.2 link	c.-15+3082T>G		intron_variant	Intron 1 of 9	ENST00000581486.6	NP_001138735.1	Q13772-1A0A024QZI5B2R5V0Q96E88
NCOA4	NM_001145260.2 link	c.22T>G	p.Phe8Val	missense_variant	Exon 2 of 12		NP_001138732.1	Q13772-4Q96E88
NCOA4	NM_001145261.2 link	c.22T>G	p.Phe8Val	missense_variant	Exon 2 of 11		NP_001138733.1	Q13772-3Q96E88

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NCOA4	ENST00000581486.6 link	c.-15+3082T>G		intron_variant	Intron 1 of 9	1	NM_001145263.2	ENSP00000462943.1		Q13772-1

Frequencies

GnomAD3 genomes

AF:

0.414

AC:

62798

AN:

151806

Hom.:

13457

Cov.:

show subpopulations

Gnomad AFR

AF:

0.353

Gnomad AMI

AF:

0.364

Gnomad AMR

AF:

0.335

Gnomad ASJ

AF:

0.447

Gnomad EAS

AF:

0.528

Gnomad SAS

AF:

0.668

Gnomad FIN

AF:

0.459

Gnomad MID

AF:

0.417

Gnomad NFE

AF:

0.433

Gnomad OTH

AF:

0.435

GnomAD2 exomes

AF:

0.445

AC:

68235

AN:

153346

AF XY:

0.464

show subpopulations

Gnomad AFR exome

AF:

0.348

Gnomad AMR exome

AF:

0.276

Gnomad ASJ exome

AF:

0.439

Gnomad EAS exome

AF:

0.524

Gnomad FIN exome

AF:

0.451

Gnomad NFE exome

AF:

0.431

Gnomad OTH exome

AF:

0.449

GnomAD4 exome

AF:

0.436

AC:

609252

AN:

1397228

Hom.:

136347

Cov.:

AF XY:

0.444

AC XY:

305680

AN XY:

689180

show subpopulations

African (AFR)

AF:

0.350

AC:

11053

AN:

31538

American (AMR)

AF:

0.288

AC:

10262

AN:

35606

Ashkenazi Jewish (ASJ)

AF:

0.434

AC:

10903

AN:

25136

East Asian (EAS)

AF:

0.527

AC:

18796

AN:

35696

South Asian (SAS)

AF:

0.653

AC:

51612

AN:

79042

European-Finnish (FIN)

AF:

0.453

AC:

22307

AN:

49192

Middle Eastern (MID)

AF:

0.440

AC:

2500

AN:

5688

European-Non Finnish (NFE)

AF:

0.424

AC:

456582

AN:

1077432

Other (OTH)

AF:

0.436

AC:

25237

AN:

57898

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.447

Heterozygous variant carriers

16664

33328

49993

66657

83321

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

14164

28328

42492

56656

70820

<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:

0.414

AC:

62836

AN:

151924

Hom.:

13464

Cov.:

AF XY:

0.421

AC XY:

31293

AN XY:

74248

show subpopulations

African (AFR)

AF:

0.353

AC:

14605

AN:

41414

American (AMR)

AF:

0.335

AC:

5116

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.447

AC:

1552

AN:

3470

East Asian (EAS)

AF:

0.528

AC:

2731

AN:

5168

South Asian (SAS)

AF:

0.667

AC:

3217

AN:

4820

European-Finnish (FIN)

AF:

0.459

AC:

4834

AN:

10538

Middle Eastern (MID)

AF:

0.403

AC:

117

AN:

290

European-Non Finnish (NFE)

AF:

0.433

AC:

29410

AN:

67934

Other (OTH)

AF:

0.438

AC:

923

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1836

3672

5509

7345

9181

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

602

1204

1806

2408

3010

<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:

0.427

Hom.:

49653

Bravo

AF:

0.395

Asia WGS

AF:

0.561

AC:

1950

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.075

BayesDel_noAF

Benign

-0.87

CADD

Benign

1.2

(source)

DANN

Benign

0.74

LIST_S2

Benign

0.20

T;T

MetaRNN

Benign

0.0047

T;T

PhyloP100

0.022

Vest4

0.033

gMVP

0.46

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