rs10740051

Variant names:

• chr10-46025670-C-T
• rs10740051
• NM_001145263.2:c.-15+4856G>A

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+4856G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.247 in 152,164 control chromosomes in the GnomAD database, including 5,515 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 0.25 (5515 hom., cov: 32)
• Consequence: NCOA4 NM_001145263.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.526
• Publications: 29 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=-0.8).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.505 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NCOA4	NM_001145263.2	c.-15+4856G>A		intron_variant	Intron 1 of 9	ENST00000581486.6	NP_001138735.1
NCOA4	NM_001145260.2	c.34+1762G>A		intron_variant	Intron 2 of 11		NP_001138732.1
NCOA4	NM_001145261.2	c.34+1762G>A		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+4856G>A		intron_variant	Intron 1 of 9	1	NM_001145263.2	ENSP00000462943.1

Frequencies

GnomAD3 genomes AF: 0.247 AC: 37582 AN: 152044 Hom.: 5511 Cov.: 32

Gnomad AFR AF: 0.111

Gnomad AMI AF: 0.230

Gnomad AMR AF: 0.223

Gnomad ASJ AF: 0.357

Gnomad EAS AF: 0.434

Gnomad SAS AF: 0.522

Gnomad FIN AF: 0.274

Gnomad MID AF: 0.291

Gnomad NFE AF: 0.291

Gnomad OTH AF: 0.287

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

GnomAD4 genome AF: 0.247 AC: 37592 AN: 152164 Hom.: 5515 Cov.: 32 AF XY: 0.254 AC XY: 18926 AN XY: 74400

African (AFR) AF: 0.111 AC: 4605 AN: 41516

American (AMR) AF: 0.223 AC: 3410 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.357 AC: 1238 AN: 3472

East Asian (EAS) AF: 0.434 AC: 2248 AN: 5174

South Asian (SAS) AF: 0.522 AC: 2516 AN: 4820

European-Finnish (FIN) AF: 0.274 AC: 2905 AN: 10588

Middle Eastern (MID) AF: 0.289 AC: 85 AN: 294

European-Non Finnish (NFE) AF: 0.291 AC: 19760 AN: 67984

Other (OTH) AF: 0.291 AC: 615 AN: 2110

Alfa AF: 0.279 Hom.: 25382

Bravo AF: 0.229

Asia WGS AF: 0.447 AC: 1554 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	1.3
DANN	Benign	0.77
PhyloP100		-0.53

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs10740051; hg19: chr10-51570152;