rs750365

chr2-217526740-C-Achr2-217526740-C-G

Variant summary

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

The NR_026597.2(DIRC3):n.1345-48182G>T 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 0.53 in 152,002 control chromosomes in the GnomAD database, including 23,836 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 0.53 (23836 hom., cov: 32)
• Consequence: DIRC3 NR_026597.2 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.53

Genes affected

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

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.768 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DIRC3	NR_026597.2	n.1345-48182G>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DIRC3	ENST00000486365.5	n.1345-48182G>T		intron_variant, non_coding_transcript_variant		5
DIRC3	ENST00000474063.5	n.322-48182G>T		intron_variant, non_coding_transcript_variant		2
DIRC3	ENST00000663562.1	n.1432-48182G>T		intron_variant, non_coding_transcript_variant
DIRC3	ENST00000676082.1	n.95-48182G>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.529 AC: 80407 AN: 151884 Hom.: 23794 Cov.: 32

Gnomad AFR AF: 0.775

Gnomad AMI AF: 0.474

Gnomad AMR AF: 0.547

Gnomad ASJ AF: 0.428

Gnomad EAS AF: 0.738

Gnomad SAS AF: 0.696

Gnomad FIN AF: 0.414

Gnomad MID AF: 0.528

Gnomad NFE AF: 0.373

Gnomad OTH AF: 0.491

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

GnomAD4 genome AF: 0.530 AC: 80507 AN: 152002 Hom.: 23836 Cov.: 32 AF XY: 0.534 AC XY: 39642 AN XY: 74302

Gnomad4 AFR AF: 0.775

Gnomad4 AMR AF: 0.548

Gnomad4 ASJ AF: 0.428

Gnomad4 EAS AF: 0.738

Gnomad4 SAS AF: 0.694

Gnomad4 FIN AF: 0.414

Gnomad4 NFE AF: 0.373

Gnomad4 OTH AF: 0.497

Alfa AF: 0.417 Hom.: 8247

Bravo AF: 0.551

Asia WGS AF: 0.719 AC: 2500 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
Cadd	Benign	0.057
Dann	Benign	0.30

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs750365; hg19: chr2-218391463;