rs1406826

Positions:

• chr20-46078725-G-A
• chr20-46078725-G-T

Variant summary

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

The NM_020967.3(NCOA5):​c.38+662C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.646 in 151,980 control chromosomes in the GnomAD database, including 33,511 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 0.65 (33511 hom., cov: 31)
• Consequence: NCOA5 NM_020967.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.06

Genes affected

NCOA5 (HGNC:15909): (nuclear receptor coactivator 5) This gene encodes a coregulator for the alpha and beta estrogen receptors and the orphan nuclear receptor NR1D2. The protein localizes to the nucleus, and is thought to have both coactivator and corepressor functions. Its interaction with nuclear receptors is independent of the AF2 domain on the receptors, which is known to regulate interaction with other coreceptors. Several alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jan 2017]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.87 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NCOA5	NM_020967.3	c.38+662C>T		intron_variant		ENST00000290231.11	NP_066018.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NCOA5	ENST00000290231.11	c.38+662C>T		intron_variant		1	NM_020967.3	ENSP00000290231.6
NCOA5	ENST00000372291.3	c.-277-8189C>T		intron_variant		3		ENSP00000361365.3

Frequencies

GnomAD3 genomes AF: 0.646 AC: 98048 AN: 151860 Hom.: 33442 Cov.: 31

Gnomad AFR AF: 0.877

Gnomad AMI AF: 0.595

Gnomad AMR AF: 0.667

Gnomad ASJ AF: 0.532

Gnomad EAS AF: 0.595

Gnomad SAS AF: 0.667

Gnomad FIN AF: 0.477

Gnomad MID AF: 0.589

Gnomad NFE AF: 0.536

Gnomad OTH AF: 0.615

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

GnomAD4 genome AF: 0.646 AC: 98180 AN: 151980 Hom.: 33511 Cov.: 31 AF XY: 0.643 AC XY: 47723 AN XY: 74268

Gnomad4 AFR AF: 0.877

Gnomad4 AMR AF: 0.668

Gnomad4 ASJ AF: 0.532

Gnomad4 EAS AF: 0.596

Gnomad4 SAS AF: 0.665

Gnomad4 FIN AF: 0.477

Gnomad4 NFE AF: 0.536

Gnomad4 OTH AF: 0.621

Alfa AF: 0.595 Hom.: 7377

Bravo AF: 0.669

Asia WGS AF: 0.685 AC: 2386 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	17
DANN	Benign	0.63

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: rs1406826; hg19: chr20-44707364;