rs41306524

Positions:

• chr10-46012928-G-A
• chr10-46012928-G-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_001145263.2(NCOA4):​c.669C>T​(p.Asp223=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.103 in 1,613,784 control chromosomes in the GnomAD database, including 8,808 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 0.091 (644 hom., cov: 32)
  • Exomes 𝑓: 0.10 (8164 hom.)
• Consequence: NCOA4 NM_001145263.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.655

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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.4).
• BP7: Synonymous conserved (PhyloP=0.655 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.108 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NCOA4	NM_001145263.2	c.669C>T	p.Asp223=	synonymous_variant	7/10	ENST00000581486.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NCOA4	ENST00000581486.6	c.669C>T	p.Asp223=	synonymous_variant	7/10	1	NM_001145263.2	P2

Frequencies

GnomAD3 genomes AF: 0.0910 AC: 13841 AN: 152108 Hom.: 645 Cov.: 32

Gnomad AFR AF: 0.0656

Gnomad AMI AF: 0.151

Gnomad AMR AF: 0.0839

Gnomad ASJ AF: 0.0805

Gnomad EAS AF: 0.0633

Gnomad SAS AF: 0.0687

Gnomad FIN AF: 0.0965

Gnomad MID AF: 0.0924

Gnomad NFE AF: 0.110

Gnomad OTH AF: 0.0942

GnomAD3 exomes AF: 0.0898 AC: 22560 AN: 251302 Hom.: 1129 AF XY: 0.0902 AC XY: 12255 AN XY: 135802

Gnomad AFR exome AF: 0.0650

Gnomad AMR exome AF: 0.0591

Gnomad ASJ exome AF: 0.0884

Gnomad EAS exome AF: 0.0484

Gnomad SAS exome AF: 0.0729

Gnomad FIN exome AF: 0.0997

Gnomad NFE exome AF: 0.111

Gnomad OTH exome AF: 0.102

GnomAD4 exome AF: 0.104 AC: 151898 AN: 1461558 Hom.: 8164 Cov.: 31 AF XY: 0.103 AC XY: 74687 AN XY: 727080

Gnomad4 AFR exome AF: 0.0650

Gnomad4 AMR exome AF: 0.0614

Gnomad4 ASJ exome AF: 0.0896

Gnomad4 EAS exome AF: 0.101

Gnomad4 SAS exome AF: 0.0730

Gnomad4 FIN exome AF: 0.101

Gnomad4 NFE exome AF: 0.110

Gnomad4 OTH exome AF: 0.0985

GnomAD4 genome AF: 0.0909 AC: 13838 AN: 152226 Hom.: 644 Cov.: 32 AF XY: 0.0895 AC XY: 6660 AN XY: 74430

Gnomad4 AFR AF: 0.0656

Gnomad4 AMR AF: 0.0837

Gnomad4 ASJ AF: 0.0805

Gnomad4 EAS AF: 0.0633

Gnomad4 SAS AF: 0.0684

Gnomad4 FIN AF: 0.0965

Gnomad4 NFE AF: 0.110

Gnomad4 OTH AF: 0.0927

Alfa AF: 0.0999 Hom.: 514

Bravo AF: 0.0884

Asia WGS AF: 0.0670 AC: 237 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.40
CADD	Benign	1.6
DANN	Benign	0.58
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs41306524; hg19: chr10-51582894;