6-125832107-T-C

Variant names:

• chr6-125832107-T-C
• rs490361
• NM_181782.5:c.50+16703T>C

Variant summary

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

The NM_181782.5(NCOA7):​c.50+16703T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.261 in 152,166 control chromosomes in the GnomAD database, including 6,292 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 0.26 (6292 hom., cov: 32)
• Consequence: NCOA7 NM_181782.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.241
• Publications: 9 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=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.42 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NCOA7	NM_181782.5	MANE Select	c.50+16703T>C		intron	N/A	NP_861447.3
	NCOA7	NM_001199619.2		c.50+16703T>C		intron	N/A	NP_001186548.1
	NCOA7	NM_001199620.2		c.50+16703T>C		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+16703T>C		intron	N/A	ENSP00000376269.2
	NCOA7	ENST00000368357.7	TSL:1	c.50+16703T>C		intron	N/A	ENSP00000357341.3
	NCOA7	ENST00000487635.1	TSL:1	n.187+16703T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.261 AC: 39634 AN: 152048 Hom.: 6286 Cov.: 32

Gnomad AFR AF: 0.0766

Gnomad AMI AF: 0.356

Gnomad AMR AF: 0.414

Gnomad ASJ AF: 0.355

Gnomad EAS AF: 0.222

Gnomad SAS AF: 0.435

Gnomad FIN AF: 0.345

Gnomad MID AF: 0.301

Gnomad NFE AF: 0.309

Gnomad OTH AF: 0.278

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

GnomAD4 genome AF: 0.261 AC: 39648 AN: 152166 Hom.: 6292 Cov.: 32 AF XY: 0.268 AC XY: 19944 AN XY: 74378

African (AFR) AF: 0.0765 AC: 3181 AN: 41558

American (AMR) AF: 0.415 AC: 6333 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.355 AC: 1231 AN: 3472

East Asian (EAS) AF: 0.222 AC: 1149 AN: 5176

South Asian (SAS) AF: 0.435 AC: 2098 AN: 4820

European-Finnish (FIN) AF: 0.345 AC: 3639 AN: 10560

Middle Eastern (MID) AF: 0.296 AC: 87 AN: 294

European-Non Finnish (NFE) AF: 0.309 AC: 21024 AN: 67986

Other (OTH) AF: 0.275 AC: 582 AN: 2114

Alfa AF: 0.295 Hom.: 5354

Bravo AF: 0.256

Asia WGS AF: 0.303 AC: 1055 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.2
DANN	Benign	0.45
PhyloP100		-0.24
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: rs490361; hg19: chr6-126153253;