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GeneBe

10-46010397-G-C

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

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

2

Clinical Significance

Benign criteria provided, single submitter B:1

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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.8).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
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_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=0.928 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
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
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAd at 3 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
NCOA4NM_001145263.2 linkuse as main transcriptc.1524C>G p.Pro508= synonymous_variant 8/10 ENST00000581486.6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
NCOA4ENST00000581486.6 linkuse as main transcriptc.1524C>G p.Pro508= synonymous_variant 8/101 NM_001145263.2 P2Q13772-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00199
AC:
302
AN:
152114
Hom.:
3
Cov.:
32
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.:
8
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.:
22
Cov.:
32
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
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00198
AC:
301
AN:
152232
Hom.:
3
Cov.:
32
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.:
0
Bravo
AF:
0.00268
Asia WGS
AF:
0.0200
AC:
68
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeJun 29, 2018- -

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.

Other links and lift over

dbSNP: rs79761167; hg19: chr10-51585425; API