Variant 10-46010397-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_001145263.2(NCOA4):c.1524C>G(p.Pro508=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00206 in 1,614,112 control chromosomes in the GnomAD database, including 25 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0020 ( 3 hom., cov: 32)

Exomes 𝑓: 0.0021 ( 22 hom. )

Consequence

NCOA4
NM_001145263.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.928

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 made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 10-46010397-G-C is Benign according to our data. Variant chr10-46010397-G-C is described in ClinVar as [Benign]. Clinvar id is 715258.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.928 with no splicing effect.

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00198 (301/152232) while in subpopulation EAS AF= 0.0189 (98/5186). AF 95% confidence interval is 0.0159. There are 3 homozygotes in gnomad4. There are 150 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NCOA4	NM_001145263.2 linkuse as main transcript	c.1524C>G	p.Pro508=	synonymous_variant	8/10	ENST00000581486.6	NP_001138735.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NCOA4	ENST00000581486.6 linkuse as main transcript	c.1524C>G	p.Pro508=	synonymous_variant	8/10	1	NM_001145263.2	ENSP00000462943	P2	Q13772-1

Frequencies

GnomAD3 genomes

AF:

0.00199

AC:

302

AN:

152114

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000435

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00445

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0190

Gnomad SAS

AF:

0.00808

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00110

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.00421

AC:

1056

AN:

251064

Hom.:

AF XY:

0.00381

AC XY:

518

AN XY:

135864

show subpopulations

Gnomad AFR exome

AF:

0.000187

Gnomad AMR exome

AF:

0.0118

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0186

Gnomad SAS exome

AF:

0.00630

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000757

Gnomad OTH exome

AF:

0.00360

GnomAD4 exome

AF:

0.00207

AC:

3019

AN:

1461880

Hom.:

Cov.:

AF XY:

0.00215

AC XY:

1564

AN XY:

727238

show subpopulations

Gnomad4 AFR exome

AF:

0.000269

Gnomad4 AMR exome

AF:

0.0108

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0135

Gnomad4 SAS exome

AF:

0.00635

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00109

Gnomad4 OTH exome

AF:

0.00384

GnomAD4 genome

AF:

0.00198

AC:

301

AN:

152232

Hom.:

Cov.:

AF XY:

0.00202

AC XY:

150

AN XY:

74424

show subpopulations

Gnomad4 AFR

AF:

0.000433

Gnomad4 AMR

AF:

0.00445

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.0189

Gnomad4 SAS

AF:

0.00809

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00110

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.000874

Hom.:

Bravo

AF:

0.00268

Asia WGS

AF:

0.0200

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jun 29, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

4.2

DANN

Benign

0.58

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over