chr10-46006241-G-A

Variant names:

• chr10-46006241-G-A
• rs11548236
• NM_001145263.2:c.*351C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001145263.2(NCOA4):​c.*351C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000366 in 327,606 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000033 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000040 (0 hom.)
• Consequence: NCOA4 NM_001145263.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00500
• Publications: 9 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NCOA4	NM_001145263.2	c.*351C>T		3_prime_UTR_variant	Exon 10 of 10	ENST00000581486.6	NP_001138735.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NCOA4	ENST00000581486.6	c.*351C>T		3_prime_UTR_variant	Exon 10 of 10	1	NM_001145263.2	ENSP00000462943.1

Frequencies

GnomAD3 genomes AF: 0.0000329 AC: 5 AN: 152114 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000829

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000399 AC: 7 AN: 175374 Hom.: 0 Cov.: 0 AF XY: 0.0000570 AC XY: 5 AN XY: 87766

African (AFR) AF: 0.00 AC: 0 AN: 7730

American (AMR) AF: 0.00 AC: 0 AN: 7752

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 7338

East Asian (EAS) AF: 0.00 AC: 0 AN: 17808

South Asian (SAS) AF: 0.000745 AC: 7 AN: 9402

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6416

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 866

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 106096

Other (OTH) AF: 0.00 AC: 0 AN: 11966

GnomAD4 genome AF: 0.0000328 AC: 5 AN: 152232 Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3 AN XY: 74426

African (AFR) AF: 0.00 AC: 0 AN: 41546

American (AMR) AF: 0.00 AC: 0 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.000830 AC: 4 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10586

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68014

Other (OTH) AF: 0.00 AC: 0 AN: 2116

Alfa AF: 0.00 Hom.: 17

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	2.2
DANN	Benign	0.72
PhyloP100		0.0050

Splicing

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

Other links and lift over

dbSNP: rs11548236; hg19: chr10-51589581;