Genetic Variant DIRC3:n.1459-19570G>C (chr2-217347722-C-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000474063.5(DIRC3):n.1459-19570G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.951 in 152,246 control chromosomes in the GnomAD database, including 69,236 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 0.95 ( 69236 hom., cov: 32)

Consequence

DIRC3
ENST00000474063.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.636

Publications

1 publications found

Variant links:

Genes affected

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

DIRC3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.993 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank
DIRC3	NR_026597.2 link	n.2291-19570G>C	intron_variant	Intron 8 of 12
DIRC3	NR_186292.1 link	n.3530-19570G>C	intron_variant	Intron 10 of 14
DIRC3	NR_186293.1 link	n.2735-19570G>C	intron_variant	Intron 12 of 16

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL
DIRC3	ENST00000474063.5 link	n.1459-19570G>C	intron_variant	Intron 7 of 11	2
DIRC3	ENST00000486365.6 link	n.2291-19570G>C	intron_variant	Intron 8 of 12	5
DIRC3	ENST00000663562.1 link	n.2378-19570G>C	intron_variant	Intron 7 of 11

Frequencies

GnomAD3 genomes

AF:

0.951

AC:

144709

AN:

152128

Hom.:

69207

Cov.:

show subpopulations

Gnomad AFR

AF:

0.831

Gnomad AMI

AF:

1.00

Gnomad AMR

AF:

0.982

Gnomad ASJ

AF:

1.00

Gnomad EAS

AF:

0.998

Gnomad SAS

AF:

1.00

Gnomad FIN

AF:

1.00

Gnomad MID

AF:

0.991

Gnomad NFE

AF:

0.999

Gnomad OTH

AF:

0.964

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

GnomAD4 genome

AF:

0.951

AC:

144792

AN:

152246

Hom.:

69236

Cov.:

AF XY:

0.953

AC XY:

70980

AN XY:

74442

show subpopulations

African (AFR)

AF:

0.830

AC:

34447

AN:

41486

American (AMR)

AF:

0.982

AC:

15013

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

1.00

AC:

3471

AN:

3472

East Asian (EAS)

AF:

0.998

AC:

5174

AN:

5186

South Asian (SAS)

AF:

1.00

AC:

4825

AN:

4826

European-Finnish (FIN)

AF:

1.00

AC:

10622

AN:

10622

Middle Eastern (MID)

AF:

0.986

AC:

290

AN:

294

European-Non Finnish (NFE)

AF:

0.999

AC:

68000

AN:

68042

Other (OTH)

AF:

0.964

AC:

2038

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

313

625

938

1250

1563

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

908

1816

2724

3632

4540

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.986

Hom.:

3490

Bravo

AF:

0.945

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

1.5

(source)

DANN

Benign

0.65

PhyloP100

-0.64

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over