rs10761581

Positions:

• chr10-46027444-A-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The ENST00000581486.6(NCOA4):​c.-15+3082T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.434 in 1,549,152 control chromosomes in the GnomAD database, including 149,811 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in Lovd as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.41 (13464 hom., cov: 32)
  • Exomes 𝑓: 0.44 (136347 hom.)
• Consequence: NCOA4 ENST00000581486.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0220

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.004737556).
• BP6: Variant 10-46027444-A-C is Benign according to our data. Variant chr10-46027444-A-C is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.648 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NCOA4	NM_001145263.2	c.-15+3082T>G		intron_variant		ENST00000581486.6	NP_001138735.1
NCOA4	NM_001145260.2	c.22T>G	p.Phe8Val	missense_variant	2/12		NP_001138732.1
NCOA4	NM_001145261.2	c.22T>G	p.Phe8Val	missense_variant	2/11		NP_001138733.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NCOA4	ENST00000581486.6	c.-15+3082T>G		intron_variant		1	NM_001145263.2	ENSP00000462943	P2

Frequencies

GnomAD3 genomes AF: 0.414 AC: 62798 AN: 151806 Hom.: 13457 Cov.: 32

Gnomad AFR AF: 0.353

Gnomad AMI AF: 0.364

Gnomad AMR AF: 0.335

Gnomad ASJ AF: 0.447

Gnomad EAS AF: 0.528

Gnomad SAS AF: 0.668

Gnomad FIN AF: 0.459

Gnomad MID AF: 0.417

Gnomad NFE AF: 0.433

Gnomad OTH AF: 0.435

GnomAD3 exomes AF: 0.445 AC: 68235 AN: 153346 Hom.: 16362 AF XY: 0.464 AC XY: 37747 AN XY: 81368

Gnomad AFR exome AF: 0.348

Gnomad AMR exome AF: 0.276

Gnomad ASJ exome AF: 0.439

Gnomad EAS exome AF: 0.524

Gnomad SAS exome AF: 0.658

Gnomad FIN exome AF: 0.451

Gnomad NFE exome AF: 0.431

Gnomad OTH exome AF: 0.449

GnomAD4 exome AF: 0.436 AC: 609252 AN: 1397228 Hom.: 136347 Cov.: 38 AF XY: 0.444 AC XY: 305680 AN XY: 689180

Gnomad4 AFR exome AF: 0.350

Gnomad4 AMR exome AF: 0.288

Gnomad4 ASJ exome AF: 0.434

Gnomad4 EAS exome AF: 0.527

Gnomad4 SAS exome AF: 0.653

Gnomad4 FIN exome AF: 0.453

Gnomad4 NFE exome AF: 0.424

Gnomad4 OTH exome AF: 0.436

GnomAD4 genome AF: 0.414 AC: 62836 AN: 151924 Hom.: 13464 Cov.: 32 AF XY: 0.421 AC XY: 31293 AN XY: 74248

Gnomad4 AFR AF: 0.353

Gnomad4 AMR AF: 0.335

Gnomad4 ASJ AF: 0.447

Gnomad4 EAS AF: 0.528

Gnomad4 SAS AF: 0.667

Gnomad4 FIN AF: 0.459

Gnomad4 NFE AF: 0.433

Gnomad4 OTH AF: 0.438

Alfa AF: 0.427 Hom.: 23901

Bravo AF: 0.395

Asia WGS AF: 0.561 AC: 1950 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.2
DANN	Benign	0.74
LIST_S2	Benign	0.20	T;T
MetaRNN	Benign	0.0047	T;T
Vest4		0.033
gMVP		0.46

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10761581; hg19: chr10-51568378;