rs41306524

Variant names:

• chr10-46012928-G-A
• rs41306524
• NM_001145263.2:c.669C>T

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_001145263.2(NCOA4):​c.669C>T​(p.Asp223Asp) 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
• Publications: 18 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 -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001145263.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NCOA4	NM_001145263.2	MANE Select	c.669C>T	p.Asp223Asp	synonymous	Exon 7 of 10	NP_001138735.1	Q13772-1
	NCOA4	NM_001145260.2		c.717C>T	p.Asp239Asp	synonymous	Exon 8 of 12	NP_001138732.1	Q13772-4
	NCOA4	NM_001145261.2		c.717C>T	p.Asp239Asp	synonymous	Exon 8 of 11	NP_001138733.1	Q13772-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NCOA4	ENST00000581486.6	TSL:1 MANE Select	c.669C>T	p.Asp223Asp	synonymous	Exon 7 of 10	ENSP00000462943.1	Q13772-1
	NCOA4	ENST00000578454.5	TSL:1	c.717C>T	p.Asp239Asp	synonymous	Exon 8 of 12	ENSP00000463027.1	Q13772-4
	NCOA4	ENST00000585132.5	TSL:1	c.669C>T	p.Asp223Asp	synonymous	Exon 7 of 10	ENSP00000464054.1	Q13772-1

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

GnomAD2 exomes AF: 0.0898 AC: 22560 AN: 251302 AF XY: 0.0902

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 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

African (AFR) AF: 0.0650 AC: 2175 AN: 33474

American (AMR) AF: 0.0614 AC: 2746 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.0896 AC: 2342 AN: 26132

East Asian (EAS) AF: 0.101 AC: 4003 AN: 39698

South Asian (SAS) AF: 0.0730 AC: 6298 AN: 86246

European-Finnish (FIN) AF: 0.101 AC: 5411 AN: 53408

Middle Eastern (MID) AF: 0.0710 AC: 409 AN: 5762

European-Non Finnish (NFE) AF: 0.110 AC: 122566 AN: 1111752

Other (OTH) AF: 0.0985 AC: 5948 AN: 60376

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

African (AFR) AF: 0.0656 AC: 2724 AN: 41550

American (AMR) AF: 0.0837 AC: 1280 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0805 AC: 279 AN: 3464

East Asian (EAS) AF: 0.0633 AC: 328 AN: 5182

South Asian (SAS) AF: 0.0684 AC: 330 AN: 4826

European-Finnish (FIN) AF: 0.0965 AC: 1023 AN: 10600

Middle Eastern (MID) AF: 0.0925 AC: 27 AN: 292

European-Non Finnish (NFE) AF: 0.110 AC: 7513 AN: 68002

Other (OTH) AF: 0.0927 AC: 196 AN: 2114

Alfa AF: 0.0987 Hom.: 677

Bravo AF: 0.0884

Asia WGS AF: 0.0670 AC: 237 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.40
CADD	Benign	1.6
DANN	Benign	0.58
PhyloP100		0.66
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

Other links and lift over

dbSNP: rs41306524; hg19: chr10-51582894;