rs529858

Variant names:

• chr6-125816778-C-A
• rs529858
• NM_181782.5:c.50+1374C>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 publications found

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-AS1 (HGNC:40954): (NCOA7 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 44 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_181782.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NCOA7	NM_181782.5	MANE Select	c.50+1374C>A		intron	N/A	NP_861447.3
	NCOA7	NM_001199619.2		c.50+1374C>A		intron	N/A	NP_001186548.1
	NCOA7	NM_001199620.2		c.50+1374C>A		intron	N/A	NP_001186549.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NCOA7	ENST00000392477.7	TSL:1 MANE Select	c.50+1374C>A		intron	N/A	ENSP00000376269.2
	NCOA7	ENST00000368357.7	TSL:1	c.50+1374C>A		intron	N/A	ENSP00000357341.3
	NCOA7	ENST00000487635.1	TSL:1	n.187+1374C>A		intron	N/A

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

African (AFR) AF: 0.00436 AC: 181 AN: 41558

American (AMR) AF: 0.0222 AC: 339 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0253 AC: 88 AN: 3472

East Asian (EAS) AF: 0.000385 AC: 2 AN: 5192

South Asian (SAS) AF: 0.0137 AC: 66 AN: 4822

European-Finnish (FIN) AF: 0.00651 AC: 69 AN: 10606

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.0254 AC: 1727 AN: 67992

Other (OTH) AF: 0.0170 AC: 36 AN: 2116

Alfa AF: 0.0235 Hom.: 91

Bravo AF: 0.0173

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	5.1
DANN	Benign	0.38
PhyloP100		0.29
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs529858; hg19: chr6-126137924;