2-217407175-T-C

Variant names:

• chr2-217407175-T-C
• rs1351164
• ENST00000474063.5:n.1458+18127A>G

Variant summary

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

The ENST00000474063.5(DIRC3):​n.1458+18127A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.245 in 152,000 control chromosomes in the GnomAD database, including 5,264 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 0.25 (5264 hom., cov: 31)
• Consequence: DIRC3 ENST00000474063.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0370
• Publications: 31 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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.576 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000474063.5. 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
	DIRC3	NR_026597.2		n.2290+18127A>G		intron	N/A
	DIRC3	NR_186292.1		n.3529+18127A>G		intron	N/A
	DIRC3	NR_186293.1		n.2734+18127A>G		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DIRC3	ENST00000474063.5	TSL:2	n.1458+18127A>G		intron	N/A
	DIRC3	ENST00000486365.6	TSL:5	n.2290+18127A>G		intron	N/A
	DIRC3	ENST00000663562.1		n.2377+18127A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.245 AC: 37243 AN: 151882 Hom.: 5251 Cov.: 31

Gnomad AFR AF: 0.239

Gnomad AMI AF: 0.127

Gnomad AMR AF: 0.311

Gnomad ASJ AF: 0.248

Gnomad EAS AF: 0.594

Gnomad SAS AF: 0.476

Gnomad FIN AF: 0.263

Gnomad MID AF: 0.294

Gnomad NFE AF: 0.190

Gnomad OTH AF: 0.248

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

GnomAD4 genome AF: 0.245 AC: 37302 AN: 152000 Hom.: 5264 Cov.: 31 AF XY: 0.254 AC XY: 18850 AN XY: 74284

African (AFR) AF: 0.240 AC: 9926 AN: 41434

American (AMR) AF: 0.311 AC: 4746 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.248 AC: 859 AN: 3470

East Asian (EAS) AF: 0.593 AC: 3053 AN: 5146

South Asian (SAS) AF: 0.476 AC: 2293 AN: 4818

European-Finnish (FIN) AF: 0.263 AC: 2771 AN: 10556

Middle Eastern (MID) AF: 0.293 AC: 86 AN: 294

European-Non Finnish (NFE) AF: 0.190 AC: 12906 AN: 67996

Other (OTH) AF: 0.260 AC: 546 AN: 2104

Alfa AF: 0.221 Hom.: 12837

Bravo AF: 0.250

Asia WGS AF: 0.542 AC: 1883 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.3
DANN	Benign	0.67
PhyloP100		-0.037

Splicing

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

Other links and lift over

dbSNP: rs1351164; hg19: chr2-218271898;