rs6088590

Variant names:

• chr20-34725762-T-C
• rs6088590
• NM_014071.5:c.6148+1497A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014071.5(NCOA6):​c.6148+1497A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.362 in 151,914 control chromosomes in the GnomAD database, including 10,201 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 0.36 (10201 hom., cov: 31)
• Consequence: NCOA6 NM_014071.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00600
• Publications: 27 publications found

Genes affected

NCOA6 (HGNC:15936): (nuclear receptor coactivator 6) The protein encoded by this gene is a transcriptional coactivator that can interact with nuclear hormone receptors to enhance their transcriptional activator functions. This protein has been shown to be involved in the hormone-dependent coactivation of several receptors, including prostanoid, retinoid, vitamin D3, thyroid hormone, and steroid receptors. Alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Jun 2011]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.388 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014071.5. 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
	NCOA6	NM_014071.5	MANE Select	c.6148+1497A>G		intron	N/A	NP_054790.2
	NCOA6	NM_001318240.1		c.6148+1497A>G		intron	N/A	NP_001305169.1	Q14686
	NCOA6	NM_001438233.1		c.6145+1497A>G		intron	N/A	NP_001425162.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NCOA6	ENST00000359003.7	TSL:1 MANE Select	c.6148+1497A>G		intron	N/A	ENSP00000351894.2	Q14686
	NCOA6	ENST00000374796.6	TSL:1	c.6148+1497A>G		intron	N/A	ENSP00000363929.2	Q14686
	NCOA6	ENST00000931656.1		c.6163+1497A>G		intron	N/A	ENSP00000601715.1

Frequencies

GnomAD3 genomes AF: 0.362 AC: 54991 AN: 151796 Hom.: 10203 Cov.: 31

Gnomad AFR AF: 0.322

Gnomad AMI AF: 0.373

Gnomad AMR AF: 0.299

Gnomad ASJ AF: 0.454

Gnomad EAS AF: 0.242

Gnomad SAS AF: 0.372

Gnomad FIN AF: 0.442

Gnomad MID AF: 0.430

Gnomad NFE AF: 0.392

Gnomad OTH AF: 0.373

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

GnomAD4 genome AF: 0.362 AC: 54999 AN: 151914 Hom.: 10201 Cov.: 31 AF XY: 0.363 AC XY: 26968 AN XY: 74244

African (AFR) AF: 0.321 AC: 13311 AN: 41404

American (AMR) AF: 0.298 AC: 4548 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.454 AC: 1575 AN: 3468

East Asian (EAS) AF: 0.242 AC: 1251 AN: 5176

South Asian (SAS) AF: 0.370 AC: 1783 AN: 4816

European-Finnish (FIN) AF: 0.442 AC: 4657 AN: 10542

Middle Eastern (MID) AF: 0.432 AC: 127 AN: 294

European-Non Finnish (NFE) AF: 0.392 AC: 26616 AN: 67948

Other (OTH) AF: 0.376 AC: 793 AN: 2110

Alfa AF: 0.375 Hom.: 6700

Bravo AF: 0.349

Asia WGS AF: 0.318 AC: 1107 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	5.2
DANN	Benign	0.86
PhyloP100		-0.0060
Mutation Taster		=100/0	polymorphism (auto)

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: rs6088590; hg19: chr20-33313566;