ENST00000486365.6:n.127-57610T>C

Variant names:

• chr2-217658439-A-G
• rs6435999
• ENST00000486365.6:n.127-57610T>C

Variant summary

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

The ENST00000486365.6(DIRC3):​n.127-57610T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.115 in 152,242 control chromosomes in the GnomAD database, including 2,878 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 0.12 (2878 hom., cov: 32)
• Consequence: DIRC3 ENST00000486365.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.34
• Publications: 5 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.355 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000486365.6. 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_026597.2		n.127-57610T>C		intron	N/A
	DIRC3	NR_186292.1		n.1366-57610T>C		intron	N/A
	DIRC3	NR_186293.1		n.1638+80045T>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DIRC3	ENST00000486365.6	TSL:5	n.127-57610T>C		intron	N/A
	DIRC3	ENST00000676082.1		n.94+98029T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.115 AC: 17440 AN: 152124 Hom.: 2859 Cov.: 32

Gnomad AFR AF: 0.359

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0464

Gnomad ASJ AF: 0.0346

Gnomad EAS AF: 0.0191

Gnomad SAS AF: 0.0821

Gnomad FIN AF: 0.00875

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0138

Gnomad OTH AF: 0.0952

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

GnomAD4 genome AF: 0.115 AC: 17513 AN: 152242 Hom.: 2878 Cov.: 32 AF XY: 0.113 AC XY: 8416 AN XY: 74442

African (AFR) AF: 0.360 AC: 14943 AN: 41520

American (AMR) AF: 0.0463 AC: 708 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0346 AC: 120 AN: 3470

East Asian (EAS) AF: 0.0193 AC: 100 AN: 5184

South Asian (SAS) AF: 0.0826 AC: 398 AN: 4820

European-Finnish (FIN) AF: 0.00875 AC: 93 AN: 10626

Middle Eastern (MID) AF: 0.0476 AC: 14 AN: 294

European-Non Finnish (NFE) AF: 0.0138 AC: 936 AN: 68014

Other (OTH) AF: 0.0952 AC: 201 AN: 2112

Alfa AF: 0.0461 Hom.: 2519

Bravo AF: 0.127

Asia WGS AF: 0.0790 AC: 276 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.30
DANN	Benign	0.54
PhyloP100		-1.3

Splicing

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

Other links and lift over

dbSNP: rs6435999; hg19: chr2-218523162;