6-125878716-C-T

Variant names:

• chr6-125878716-C-T
• rs1570383
• NM_181782.5:c.459+346C>T

Variant summary

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

The NM_181782.5(NCOA7):​c.459+346C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.241 in 152,030 control chromosomes in the GnomAD database, including 4,999 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 0.24 (4999 hom., cov: 32)
• Consequence: NCOA7 NM_181782.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0540
• Publications: 7 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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.383 is higher than 0.05.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NCOA7	NM_181782.5	MANE Select	c.459+346C>T		intron	N/A	NP_861447.3
	NCOA7	NM_001199619.2		c.459+346C>T		intron	N/A	NP_001186548.1	Q8NI08-1
	NCOA7	NM_001199620.2		c.459+346C>T		intron	N/A	NP_001186549.1	Q8NI08-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NCOA7	ENST00000392477.7	TSL:1 MANE Select	c.459+346C>T		intron	N/A	ENSP00000376269.2	Q8NI08-1
	NCOA7	ENST00000368357.7	TSL:1	c.459+346C>T		intron	N/A	ENSP00000357341.3	Q8NI08-1
	NCOA7	ENST00000867852.1		c.459+346C>T		intron	N/A	ENSP00000537911.1

Frequencies

GnomAD3 genomes AF: 0.241 AC: 36583 AN: 151912 Hom.: 4997 Cov.: 32

Gnomad AFR AF: 0.388

Gnomad AMI AF: 0.275

Gnomad AMR AF: 0.142

Gnomad ASJ AF: 0.147

Gnomad EAS AF: 0.247

Gnomad SAS AF: 0.134

Gnomad FIN AF: 0.204

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.191

Gnomad OTH AF: 0.216

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

GnomAD4 genome AF: 0.241 AC: 36604 AN: 152030 Hom.: 4999 Cov.: 32 AF XY: 0.239 AC XY: 17745 AN XY: 74320

African (AFR) AF: 0.388 AC: 16082 AN: 41458

American (AMR) AF: 0.142 AC: 2164 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.147 AC: 511 AN: 3470

East Asian (EAS) AF: 0.247 AC: 1275 AN: 5162

South Asian (SAS) AF: 0.134 AC: 645 AN: 4818

European-Finnish (FIN) AF: 0.204 AC: 2157 AN: 10550

Middle Eastern (MID) AF: 0.228 AC: 67 AN: 294

European-Non Finnish (NFE) AF: 0.191 AC: 13000 AN: 67984

Other (OTH) AF: 0.214 AC: 452 AN: 2110

Alfa AF: 0.203 Hom.: 14940

Bravo AF: 0.246

Asia WGS AF: 0.202 AC: 703 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	5.7
DANN	Benign	0.68
PhyloP100		0.054
Mutation Taster		=100/0	polymorphism (auto)

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: rs1570383; hg19: chr6-126199862; COSMIC: COSV57659683; COSMIC: COSV57659683;