rs529858

Positions:

• chr6-125816778-C-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_181782.5(NCOA7):​c.50+1374C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0168 in 152,264 control chromosomes in the GnomAD database, including 44 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 0.017 (44 hom., cov: 32)
• Consequence: NCOA7 NM_181782.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.288

Genes affected

NCOA7 (HGNC:21081): (nuclear receptor coactivator 7) Enables nuclear receptor binding activity and nuclear receptor coactivator activity. Involved in positive regulation of transcription by RNA polymerase II. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

NCOA7 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0168 (2560/152264) while in subpopulation NFE AF= 0.0254 (1727/67992). AF 95% confidence interval is 0.0244. There are 44 homozygotes in gnomad4. There are 1197 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 44 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NCOA7	NM_181782.5	c.50+1374C>A		intron_variant		ENST00000392477.7	NP_861447.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NCOA7	ENST00000392477.7	c.50+1374C>A		intron_variant		1	NM_181782.5	ENSP00000376269.2

Frequencies

GnomAD3 genomes AF: 0.0168 AC: 2560 AN: 152146 Hom.: 44 Cov.: 32

Gnomad AFR AF: 0.00437

Gnomad AMI AF: 0.0493

Gnomad AMR AF: 0.0222

Gnomad ASJ AF: 0.0253

Gnomad EAS AF: 0.000384

Gnomad SAS AF: 0.0135

Gnomad FIN AF: 0.00651

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0254

Gnomad OTH AF: 0.0172

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

GnomAD4 genome AF: 0.0168 AC: 2560 AN: 152264 Hom.: 44 Cov.: 32 AF XY: 0.0161 AC XY: 1197 AN XY: 74448

Gnomad4 AFR AF: 0.00436

Gnomad4 AMR AF: 0.0222

Gnomad4 ASJ AF: 0.0253

Gnomad4 EAS AF: 0.000385

Gnomad4 SAS AF: 0.0137

Gnomad4 FIN AF: 0.00651

Gnomad4 NFE AF: 0.0254

Gnomad4 OTH AF: 0.0170

Alfa AF: 0.0232 Hom.: 30

Bravo AF: 0.0173

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	5.1
DANN	Benign	0.38

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: rs529858; hg19: chr6-126137924;