rs10761618

chr10-46021216-A-Gchr10-46021216-A-T

Variant summary

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

The NM_001145263.2(NCOA4):c.-14-4522T>C 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 152,180 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: 33)
• Consequence: NCOA4 NM_001145263.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.85

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=-0.47).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.503 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NCOA4	NM_001145263.2	c.-14-4522T>C		intron_variant		ENST00000581486.6
NCOA4	NM_001145260.2	c.35-4522T>C		intron_variant
NCOA4	NM_001145261.2	c.35-4522T>C		intron_variant
NCOA4	NM_005437.4	c.-15+2114T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NCOA4	ENST00000581486.6	c.-14-4522T>C		intron_variant		1	NM_001145263.2	P2

Frequencies

GnomAD3 genomes AF: 0.247 AC: 37582 AN: 152062 Hom.: 5511 Cov.: 33

Gnomad AFR AF: 0.111

Gnomad AMI AF: 0.230

Gnomad AMR AF: 0.223

Gnomad ASJ AF: 0.358

Gnomad EAS AF: 0.434

Gnomad SAS AF: 0.520

Gnomad FIN AF: 0.274

Gnomad MID AF: 0.291

Gnomad NFE AF: 0.291

Gnomad OTH AF: 0.288

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

GnomAD4 genome AF: 0.247 AC: 37592 AN: 152180 Hom.: 5515 Cov.: 33 AF XY: 0.254 AC XY: 18921 AN XY: 74408

Gnomad4 AFR AF: 0.111

Gnomad4 AMR AF: 0.222

Gnomad4 ASJ AF: 0.358

Gnomad4 EAS AF: 0.434

Gnomad4 SAS AF: 0.520

Gnomad4 FIN AF: 0.274

Gnomad4 NFE AF: 0.291

Gnomad4 OTH AF: 0.293

Alfa AF: 0.283 Hom.: 5048

Bravo AF: 0.229

Asia WGS AF: 0.446 AC: 1548 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
Cadd	Benign	14
Dann	Benign	0.94

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: rs10761618; hg19: chr10-51574606;