chr20-34700707-G-C

Position:

• chr20-34700707-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000628752.2(NCOA6):​c.558-3464C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.356 in 152,096 control chromosomes in the GnomAD database, including 9,908 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 (9908 hom., cov: 31)
• Consequence: NCOA6 ENST00000628752.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.70

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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.394 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NCOA6	ENST00000628752.2	c.558-3464C>G		intron_variant		5		ENSP00000486894
NCOA6	ENST00000434040.5	n.40-1859C>G		intron_variant, non_coding_transcript_variant		3
NCOA6	ENST00000593786.1	n.568-1859C>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.356 AC: 54166 AN: 151978 Hom.: 9911 Cov.: 31

Gnomad AFR AF: 0.293

Gnomad AMI AF: 0.372

Gnomad AMR AF: 0.300

Gnomad ASJ AF: 0.453

Gnomad EAS AF: 0.241

Gnomad SAS AF: 0.357

Gnomad FIN AF: 0.443

Gnomad MID AF: 0.424

Gnomad NFE AF: 0.398

Gnomad OTH AF: 0.355

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

GnomAD4 genome AF: 0.356 AC: 54174 AN: 152096 Hom.: 9908 Cov.: 31 AF XY: 0.357 AC XY: 26505 AN XY: 74330

Gnomad4 AFR AF: 0.293

Gnomad4 AMR AF: 0.299

Gnomad4 ASJ AF: 0.453

Gnomad4 EAS AF: 0.240

Gnomad4 SAS AF: 0.355

Gnomad4 FIN AF: 0.443

Gnomad4 NFE AF: 0.398

Gnomad4 OTH AF: 0.358

Alfa AF: 0.390 Hom.: 1486

Bravo AF: 0.342

Asia WGS AF: 0.306 AC: 1066 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.42
DANN	Benign	0.75

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs6087619; hg19: chr20-33288511;