rs6088590

Positions:

• chr20-34725762-T-C

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NCOA6	NM_014071.5	c.6148+1497A>G		intron_variant		ENST00000359003.7	NP_054790.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NCOA6	ENST00000359003.7	c.6148+1497A>G		intron_variant		1	NM_014071.5	ENSP00000351894

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

Gnomad4 AFR AF: 0.321

Gnomad4 AMR AF: 0.298

Gnomad4 ASJ AF: 0.454

Gnomad4 EAS AF: 0.242

Gnomad4 SAS AF: 0.370

Gnomad4 FIN AF: 0.442

Gnomad4 NFE AF: 0.392

Gnomad4 OTH AF: 0.376

Alfa AF: 0.376 Hom.: 5751

Bravo AF: 0.349

Asia WGS AF: 0.318 AC: 1107 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	5.2
DANN	Benign	0.86

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: rs6088590; hg19: chr20-33313566;