rs16857609

chr2-217431785-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NR_026597.2(DIRC3):n.1790+1138G>A variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.283 in 152,048 control chromosomes in the GnomAD database, including 6,747 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 0.28 (6747 hom., cov: 31)
• Consequence: DIRC3 NR_026597.2 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.339

Genes affected

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

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.37).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.577 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DIRC3	NR_026597.2	n.1790+1138G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DIRC3	ENST00000486365.5	n.1790+1138G>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.283 AC: 43050 AN: 151930 Hom.: 6734 Cov.: 31

Gnomad AFR AF: 0.238

Gnomad AMI AF: 0.282

Gnomad AMR AF: 0.328

Gnomad ASJ AF: 0.273

Gnomad EAS AF: 0.596

Gnomad SAS AF: 0.550

Gnomad FIN AF: 0.300

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.257

Gnomad OTH AF: 0.269

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

GnomAD4 genome AF: 0.283 AC: 43099 AN: 152048 Hom.: 6747 Cov.: 31 AF XY: 0.290 AC XY: 21543 AN XY: 74312

Gnomad4 AFR AF: 0.238

Gnomad4 AMR AF: 0.328

Gnomad4 ASJ AF: 0.273

Gnomad4 EAS AF: 0.595

Gnomad4 SAS AF: 0.550

Gnomad4 FIN AF: 0.300

Gnomad4 NFE AF: 0.257

Gnomad4 OTH AF: 0.279

Alfa AF: 0.266 Hom.: 1323

Bravo AF: 0.284

Asia WGS AF: 0.555 AC: 1932 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.37
Cadd	Benign	15
Dann	Benign	0.87

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs16857609; hg19: chr2-218296508;