rs4463801

chr10-46010070-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001145263.2(NCOA4):c.1698+153C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.405 in 152,042 control chromosomes in the GnomAD database, including 12,973 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 0.41 (12973 hom., cov: 32)
• Consequence: NCOA4 NM_001145263.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.227

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.638 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NCOA4	NM_001145263.2	c.1698+153C>T		intron_variant		ENST00000581486.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NCOA4	ENST00000581486.6	c.1698+153C>T		intron_variant		1	NM_001145263.2	P2

Frequencies

GnomAD3 genomes AF: 0.405 AC: 61583 AN: 151924 Hom.: 12969 Cov.: 32

Gnomad AFR AF: 0.341

Gnomad AMI AF: 0.363

Gnomad AMR AF: 0.324

Gnomad ASJ AF: 0.446

Gnomad EAS AF: 0.474

Gnomad SAS AF: 0.658

Gnomad FIN AF: 0.446

Gnomad MID AF: 0.418

Gnomad NFE AF: 0.431

Gnomad OTH AF: 0.428

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

GnomAD4 genome AF: 0.405 AC: 61618 AN: 152042 Hom.: 12973 Cov.: 32 AF XY: 0.412 AC XY: 30636 AN XY: 74292

Gnomad4 AFR AF: 0.341

Gnomad4 AMR AF: 0.324

Gnomad4 ASJ AF: 0.446

Gnomad4 EAS AF: 0.475

Gnomad4 SAS AF: 0.657

Gnomad4 FIN AF: 0.446

Gnomad4 NFE AF: 0.431

Gnomad4 OTH AF: 0.430

Alfa AF: 0.408 Hom.: 1579

Bravo AF: 0.386

Asia WGS AF: 0.532 AC: 1847 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	1.6
Dann	Benign	0.55

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

Other links and lift over

dbSNP: rs4463801; hg19: chr10-51585752;