rs6088619

Variant names:

• chr20-34824068-A-G
• rs6088619
• NM_014071.5:c.-164+1404T>C

Variant summary

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

The NM_014071.5(NCOA6):​c.-164+1404T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0852 in 152,310 control chromosomes in the GnomAD database, including 772 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 0.085 (772 hom., cov: 32)
• Consequence: NCOA6 NM_014071.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.394
• Publications: 28 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=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.128 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NCOA6	NM_014071.5	c.-164+1404T>C		intron_variant	Intron 1 of 14	ENST00000359003.7	NP_054790.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NCOA6	ENST00000359003.7	c.-164+1404T>C		intron_variant	Intron 1 of 14	1	NM_014071.5	ENSP00000351894.2
NCOA6	ENST00000612493.4	c.-164+1404T>C		intron_variant	Intron 1 of 13	5		ENSP00000481177.1
NCOA6	ENST00000616167.1	c.-164+1404T>C		intron_variant	Intron 1 of 10	5		ENSP00000481935.1

Frequencies

GnomAD3 genomes AF: 0.0853 AC: 12979 AN: 152192 Hom.: 772 Cov.: 32

Gnomad AFR AF: 0.0222

Gnomad AMI AF: 0.140

Gnomad AMR AF: 0.0775

Gnomad ASJ AF: 0.0816

Gnomad EAS AF: 0.000577

Gnomad SAS AF: 0.0234

Gnomad FIN AF: 0.123

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.130

Gnomad OTH AF: 0.0836

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

GnomAD4 genome AF: 0.0852 AC: 12981 AN: 152310 Hom.: 772 Cov.: 32 AF XY: 0.0826 AC XY: 6153 AN XY: 74472

African (AFR) AF: 0.0221 AC: 919 AN: 41582

American (AMR) AF: 0.0774 AC: 1185 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0816 AC: 283 AN: 3470

East Asian (EAS) AF: 0.000578 AC: 3 AN: 5190

South Asian (SAS) AF: 0.0236 AC: 114 AN: 4822

European-Finnish (FIN) AF: 0.123 AC: 1306 AN: 10614

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.130 AC: 8859 AN: 68008

Other (OTH) AF: 0.0827 AC: 175 AN: 2116

Alfa AF: 0.107 Hom.: 2354

Bravo AF: 0.0789

Asia WGS AF: 0.0120 AC: 42 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	4.1
DANN	Benign	0.46
PhyloP100		0.39
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs6088619; hg19: chr20-33411871;