rs549438

Positions:

• chr6-125813790-G-A
• chr6-125813790-G-T

Variant summary

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

The NM_181782.5(NCOA7):​c.-64-1501G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.587 in 151,932 control chromosomes in the GnomAD database, including 30,475 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 0.59 (30475 hom., cov: 31)
• Consequence: NCOA7 NM_181782.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0320

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.852 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NCOA7	NM_181782.5	c.-64-1501G>A		intron_variant		ENST00000392477.7	NP_861447.3
NCOA7-AS1	NR_126386.1	n.49+5020C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NCOA7	ENST00000392477.7	c.-64-1501G>A		intron_variant		1	NM_181782.5	ENSP00000376269
NCOA7-AS1	ENST00000429007.1	n.49+5020C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.587 AC: 89109 AN: 151814 Hom.: 30467 Cov.: 31

Gnomad AFR AF: 0.203

Gnomad AMI AF: 0.656

Gnomad AMR AF: 0.760

Gnomad ASJ AF: 0.679

Gnomad EAS AF: 0.873

Gnomad SAS AF: 0.817

Gnomad FIN AF: 0.736

Gnomad MID AF: 0.634

Gnomad NFE AF: 0.712

Gnomad OTH AF: 0.641

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

GnomAD4 genome AF: 0.587 AC: 89131 AN: 151932 Hom.: 30475 Cov.: 31 AF XY: 0.595 AC XY: 44162 AN XY: 74276

Gnomad4 AFR AF: 0.203

Gnomad4 AMR AF: 0.761

Gnomad4 ASJ AF: 0.679

Gnomad4 EAS AF: 0.873

Gnomad4 SAS AF: 0.817

Gnomad4 FIN AF: 0.736

Gnomad4 NFE AF: 0.712

Gnomad4 OTH AF: 0.645

Alfa AF: 0.697 Hom.: 49460

Bravo AF: 0.572

Asia WGS AF: 0.791 AC: 2747 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.74
DANN	Benign	0.64

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: rs549438; hg19: chr6-126134936;