rs3813713

Variant names:

• chr10-46024691-G-C
• rs3813713
• NM_001145263.2:c.-15+5835C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001145263.2(NCOA4):​c.-15+5835C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0527 in 152,274 control chromosomes in the GnomAD database, including 250 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 0.053 (250 hom., cov: 33)
• Consequence: NCOA4 NM_001145263.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.585
• Publications: 6 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0738 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NCOA4	NM_001145263.2	c.-15+5835C>G		intron_variant	Intron 1 of 9	ENST00000581486.6	NP_001138735.1
NCOA4	NM_001145260.2	c.34+2741C>G		intron_variant	Intron 2 of 11		NP_001138732.1
NCOA4	NM_001145261.2	c.34+2741C>G		intron_variant	Intron 2 of 10		NP_001138733.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NCOA4	ENST00000581486.6	c.-15+5835C>G		intron_variant	Intron 1 of 9	1	NM_001145263.2	ENSP00000462943.1

Frequencies

GnomAD3 genomes AF: 0.0527 AC: 8023 AN: 152156 Hom.: 250 Cov.: 33

Gnomad AFR AF: 0.0167

Gnomad AMI AF: 0.128

Gnomad AMR AF: 0.0510

Gnomad ASJ AF: 0.0594

Gnomad EAS AF: 0.0208

Gnomad SAS AF: 0.0514

Gnomad FIN AF: 0.0563

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0755

Gnomad OTH AF: 0.0584

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0527 AC: 8020 AN: 152274 Hom.: 250 Cov.: 33 AF XY: 0.0513 AC XY: 3819 AN XY: 74464

African (AFR) AF: 0.0166 AC: 692 AN: 41570

American (AMR) AF: 0.0509 AC: 779 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0594 AC: 206 AN: 3470

East Asian (EAS) AF: 0.0208 AC: 108 AN: 5186

South Asian (SAS) AF: 0.0512 AC: 247 AN: 4824

European-Finnish (FIN) AF: 0.0563 AC: 596 AN: 10594

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.0755 AC: 5134 AN: 68014

Other (OTH) AF: 0.0573 AC: 121 AN: 2112

Alfa AF: 0.0606 Hom.: 47

Bravo AF: 0.0499

Asia WGS AF: 0.0350 AC: 125 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	6.4
DANN	Benign	0.64
PhyloP100		0.58

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

Other links and lift over

dbSNP: rs3813713; hg19: chr10-51571131;