Variant 10-46010599-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBS1BS2

The NM_001145263.2(NCOA4):c.1322G>A(p.Gly441Glu) variant causes a missense change. The variant allele was found at a frequency of 0.00259 in 1,614,160 control chromosomes in the GnomAD database, including 30 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0047 ( 5 hom., cov: 32)

Exomes 𝑓: 0.0024 ( 25 hom. )

Consequence

NCOA4
NM_001145263.2 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 5.66

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 made for transcript

Verdict is Benign. Variant got -18 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.14201319).

BP6

Variant 10-46010599-C-T is Benign according to our data. Variant chr10-46010599-C-T is described in ClinVar as [Benign]. Clinvar id is 714454.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00473 (721/152276) while in subpopulation EAS AF= 0.0189 (98/5190). AF 95% confidence interval is 0.0159. There are 5 homozygotes in gnomad4. There are 342 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NCOA4	NM_001145263.2 linkuse as main transcript	c.1322G>A	p.Gly441Glu	missense_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.1322G>A	p.Gly441Glu	missense_variant	8/10	1	NM_001145263.2	ENSP00000462943	P2	Q13772-1

Frequencies

GnomAD3 genomes

AF:

0.00473

AC:

720

AN:

152158

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0100

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00550

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0190

Gnomad SAS

AF:

0.00827

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00110

Gnomad OTH

AF:

0.00335

GnomAD3 exomes

AF:

0.00486

AC:

1220

AN:

251282

Hom.:

AF XY:

0.00425

AC XY:

577

AN XY:

135876

show subpopulations

Gnomad AFR exome

AF:

0.00910

Gnomad AMR exome

AF:

0.0120

Gnomad ASJ exome

AF:

0.0000992

Gnomad EAS exome

AF:

0.0186

Gnomad SAS exome

AF:

0.00634

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000844

Gnomad OTH exome

AF:

0.00376

GnomAD4 exome

AF:

0.00237

AC:

3466

AN:

1461884

Hom.:

Cov.:

AF XY:

0.00242

AC XY:

1762

AN XY:

727240

show subpopulations

Gnomad4 AFR exome

AF:

0.00989

Gnomad4 AMR exome

AF:

0.0112

Gnomad4 ASJ exome

AF:

0.0000765

Gnomad4 EAS exome

AF:

0.0135

Gnomad4 SAS exome

AF:

0.00636

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00114

Gnomad4 OTH exome

AF:

0.00449

GnomAD4 genome

AF:

0.00473

AC:

721

AN:

152276

Hom.:

Cov.:

AF XY:

0.00459

AC XY:

342

AN XY:

74470

show subpopulations

Gnomad4 AFR

AF:

0.0100

Gnomad4 AMR

AF:

0.00549

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.0189

Gnomad4 SAS

AF:

0.00828

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00110

Gnomad4 OTH

AF:

0.00331

Alfa

AF:

0.00216

Hom.:

Bravo

AF:

0.00583

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

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.84

BayesDel_noAF

Pathogenic

0.37

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.53

D;D;T;D;.;.;.

LIST_S2

Uncertain

0.95

.;D;D;.;D;D;D

MetaRNN

Benign

0.14

T;T;T;T;T;T;T

Sift4G

Pathogenic

0.0

D;D;D;D;D;D;D

Vest4

0.75

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

gMVP

0.87

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