rs674859

Positions:

• chr6-125842391-C-T

Variant summary

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

The NM_181782.5(NCOA7):​c.51-12629C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.319 in 151,988 control chromosomes in the GnomAD database, including 7,875 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 0.32 (7875 hom., cov: 32)
• Consequence: NCOA7 NM_181782.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.24

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.427 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NCOA7	NM_181782.5	c.51-12629C>T		intron_variant		ENST00000392477.7	NP_861447.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NCOA7	ENST00000392477.7	c.51-12629C>T		intron_variant		1	NM_181782.5	ENSP00000376269

Frequencies

GnomAD3 genomes AF: 0.319 AC: 48384 AN: 151870 Hom.: 7863 Cov.: 32

Gnomad AFR AF: 0.271

Gnomad AMI AF: 0.360

Gnomad AMR AF: 0.432

Gnomad ASJ AF: 0.370

Gnomad EAS AF: 0.256

Gnomad SAS AF: 0.442

Gnomad FIN AF: 0.346

Gnomad MID AF: 0.307

Gnomad NFE AF: 0.310

Gnomad OTH AF: 0.326

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

GnomAD4 genome AF: 0.319 AC: 48430 AN: 151988 Hom.: 7875 Cov.: 32 AF XY: 0.325 AC XY: 24142 AN XY: 74282

Gnomad4 AFR AF: 0.271

Gnomad4 AMR AF: 0.433

Gnomad4 ASJ AF: 0.370

Gnomad4 EAS AF: 0.256

Gnomad4 SAS AF: 0.442

Gnomad4 FIN AF: 0.346

Gnomad4 NFE AF: 0.310

Gnomad4 OTH AF: 0.323

Alfa AF: 0.321 Hom.: 6676

Bravo AF: 0.321

Asia WGS AF: 0.323 AC: 1124 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	5.1
DANN	Benign	0.65

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: rs674859; hg19: chr6-126163537;