Variant chr10-46010661-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_001145263.2(NCOA4):c.1260G>A(p.Glu420Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00414 in 1,614,168 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.0032 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0042 ( 25 hom. )

Consequence

NCOA4
NM_001145263.2 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.312

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 -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.55).

BP6

Variant 10-46010661-C-T is Benign according to our data. Variant chr10-46010661-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2640465.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.312 with no splicing effect.

BS2

High Homozygotes in GnomAdExome4 at 25 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NCOA4	NM_001145263.2 linkuse as main transcript	c.1260G>A	p.Glu420Glu	synonymous_variant	8/10	ENST00000581486.6	NP_001138735.1	Q13772-1A0A024QZI5B2R5V0Q96E88

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NCOA4	ENST00000581486.6 linkuse as main transcript	c.1260G>A	p.Glu420Glu	synonymous_variant	8/10	1	NM_001145263.2	ENSP00000462943.1		Q13772-1

Frequencies

GnomAD3 genomes

AF:

0.00315

AC:

480

AN:

152172

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000869

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00314

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00518

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00531

Gnomad OTH

AF:

0.00382

GnomAD3 exomes

AF:

0.00270

AC:

679

AN:

251384

Hom.:

AF XY:

0.00296

AC XY:

402

AN XY:

135858

show subpopulations

Gnomad AFR exome

AF:

0.000615

Gnomad AMR exome

AF:

0.00121

Gnomad ASJ exome

AF:

0.0000992

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00405

Gnomad FIN exome

AF:

0.000323

Gnomad NFE exome

AF:

0.00422

Gnomad OTH exome

AF:

0.00245

GnomAD4 exome

AF:

0.00424

AC:

6199

AN:

1461878

Hom.:

Cov.:

AF XY:

0.00435

AC XY:

3162

AN XY:

727238

show subpopulations

Gnomad4 AFR exome

AF:

0.000508

Gnomad4 AMR exome

AF:

0.00116

Gnomad4 ASJ exome

AF:

0.000115

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00467

Gnomad4 FIN exome

AF:

0.000468

Gnomad4 NFE exome

AF:

0.00494

Gnomad4 OTH exome

AF:

0.00339

GnomAD4 genome

AF:

0.00315

AC:

480

AN:

152290

Hom.:

Cov.:

AF XY:

0.00326

AC XY:

243

AN XY:

74454

show subpopulations

Gnomad4 AFR

AF:

0.000866

Gnomad4 AMR

AF:

0.00314

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00518

Gnomad4 FIN

AF:

0.000188

Gnomad4 NFE

AF:

0.00531

Gnomad4 OTH

AF:

0.00378

Alfa

AF:

0.00384

Hom.:

Bravo

AF:

0.00268

Asia WGS

AF:

0.00144

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Dec 01, 2022

NCOA4: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.55

CADD

Benign

4.8

DANN

Benign

0.68

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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