NR_186293.1:n.547-18590G>A

Variant names:

• chr2-217758165-C-T
• rs7576189
• NR_186293.1:n.547-18590G>A

Variant summary

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

The NR_186293.1(DIRC3):​n.547-18590G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.938 in 152,174 control chromosomes in the GnomAD database, including 67,000 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 0.94 (67000 hom., cov: 30)
• Consequence: DIRC3 NR_186293.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.182
• Publications: 3 publications found

Genes affected

DIRC3 (HGNC:17805): (disrupted in renal carcinoma 3)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NR_186293.1. 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
	DIRC3	NR_186293.1		n.547-18590G>A		intron	N/A
	DIRC3	NR_186296.1		n.476+24341G>A		intron	N/A
	DIRC3	NR_186298.1		n.476+24341G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Frequencies

GnomAD3 genomes AF: 0.938 AC: 142608 AN: 152056 Hom.: 66953 Cov.: 30

Gnomad AFR AF: 0.910

Gnomad AMI AF: 0.818

Gnomad AMR AF: 0.954

Gnomad ASJ AF: 0.925

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.961

Gnomad FIN AF: 0.965

Gnomad MID AF: 0.924

Gnomad NFE AF: 0.943

Gnomad OTH AF: 0.940

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

GnomAD4 genome AF: 0.938 AC: 142713 AN: 152174 Hom.: 67000 Cov.: 30 AF XY: 0.941 AC XY: 69971 AN XY: 74384

African (AFR) AF: 0.910 AC: 37751 AN: 41492

American (AMR) AF: 0.955 AC: 14591 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.925 AC: 3210 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5175 AN: 5176

South Asian (SAS) AF: 0.961 AC: 4626 AN: 4814

European-Finnish (FIN) AF: 0.965 AC: 10232 AN: 10606

Middle Eastern (MID) AF: 0.922 AC: 271 AN: 294

European-Non Finnish (NFE) AF: 0.943 AC: 64124 AN: 68010

Other (OTH) AF: 0.941 AC: 1989 AN: 2114

Alfa AF: 0.944 Hom.: 10413

Bravo AF: 0.934

Asia WGS AF: 0.976 AC: 3394 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.88
DANN	Benign	0.76
PhyloP100		-0.18

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs7576189; hg19: chr2-218622888;