rs4463801

Variant names:

• chr10-46010070-G-A
• rs4463801
• NM_001145263.2:c.1698+153C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 11 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=-0.91).
• 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 rank	MANE	Protein	UniProt
NCOA4	NM_001145263.2	c.1698+153C>T		intron_variant	Intron 8 of 9	ENST00000581486.6	NP_001138735.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NCOA4	ENST00000581486.6	c.1698+153C>T		intron_variant	Intron 8 of 9	1	NM_001145263.2	ENSP00000462943.1

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

African (AFR) AF: 0.341 AC: 14152 AN: 41464

American (AMR) AF: 0.324 AC: 4944 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.446 AC: 1548 AN: 3468

East Asian (EAS) AF: 0.475 AC: 2458 AN: 5178

South Asian (SAS) AF: 0.657 AC: 3166 AN: 4818

European-Finnish (FIN) AF: 0.446 AC: 4699 AN: 10542

Middle Eastern (MID) AF: 0.405 AC: 119 AN: 294

European-Non Finnish (NFE) AF: 0.431 AC: 29292 AN: 67972

Other (OTH) AF: 0.430 AC: 909 AN: 2112

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
PhyloP100		-0.23

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: rs4463801; hg19: chr10-51585752;