Genetic Variant CAP1P1:n.223G>A (chr3-76434240-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000476047.1(CAP1P1):n.223G>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0236 in 1,015,188 control chromosomes in the GnomAD database, including 781 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 0.024 ( 90 hom., cov: 32)

Exomes 𝑓: 0.023 ( 691 hom. )

Consequence

CAP1P1
ENST00000476047.1 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.80

Publications

0 publications found

Variant links:

Genes affected

CAP1P1 (HGNC:31134): (CAP1 pseudogene 1)

CAP1P1 links:

ROBO2 (HGNC:10250): (roundabout guidance receptor 2) The protein encoded by this gene belongs to the ROBO family, part of the immunoglobulin superfamily of proteins that are highly conserved from fly to human. The encoded protein is a transmembrane receptor for the slit homolog 2 protein and functions in axon guidance and cell migration. Mutations in this gene are associated with vesicoureteral reflux, characterized by the backward flow of urine from the bladder into the ureters or the kidney. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2014]

ROBO2 Gene-Disease associations (from GenCC):

vesicoureteral reflux 2
Inheritance: AD Classification: STRONG Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
familial vesicoureteral reflux
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ROBO2 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=-0.75).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0977 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	Protein
CAP1P1		n.76434240G>A	intragenic_variant
ROBO2	NM_001394212.1 link	c.130+122823G>A	intron_variant	Intron 1 of 27	NP_001381141.1
ROBO2	NM_001378191.1 link	c.109+496638G>A	intron_variant	Intron 2 of 29	NP_001365120.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	Protein	UniProt
CAP1P1	ENST00000476047.1 link	n.223G>A	non_coding_transcript_exon_variant	Exon 1 of 1	6
ROBO2	ENST00000696630.1 link	c.109+496638G>A	intron_variant	Intron 2 of 29		ENSP00000512767.1	A0A8Q3SIW8
ROBO2	ENST00000696629.1 link	c.109+496638G>A	intron_variant	Intron 2 of 28		ENSP00000512766.1	A0A8Q3SIU0

Frequencies

GnomAD3 genomes

AF:

0.0243

AC:

3692

AN:

152192

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0330

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0472

Gnomad ASJ

AF:

0.0499

Gnomad EAS

AF:

0.0278

Gnomad SAS

AF:

0.105

Gnomad FIN

AF:

0.00141

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.0104

Gnomad OTH

AF:

0.0220

GnomAD4 exome

AF:

0.0234

AC:

20229

AN:

862878

Hom.:

691

Cov.:

AF XY:

0.0260

AC XY:

11777

AN XY:

453682

show subpopulations

African (AFR)

AF:

0.0346

AC:

761

AN:

21988

American (AMR)

AF:

0.0739

AC:

3252

AN:

43984

Ashkenazi Jewish (ASJ)

AF:

0.0503

AC:

1130

AN:

22474

East Asian (EAS)

AF:

0.0343

AC:

1268

AN:

37000

South Asian (SAS)

AF:

0.0960

AC:

7121

AN:

74198

European-Finnish (FIN)

AF:

0.00152

AC:

AN:

53222

Middle Eastern (MID)

AF:

0.0361

AC:

151

AN:

4184

European-Non Finnish (NFE)

AF:

0.00958

AC:

5411

AN:

565072

Other (OTH)

AF:

0.0259

AC:

1054

AN:

40756

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

1204

2408

3612

4816

6020

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

234

468

702

936

1170

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0244

AC:

3716

AN:

152310

Hom.:

Cov.:

AF XY:

0.0264

AC XY:

1964

AN XY:

74472

show subpopulations

African (AFR)

AF:

0.0333

AC:

1386

AN:

41570

American (AMR)

AF:

0.0473

AC:

723

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.0499

AC:

173

AN:

3470

East Asian (EAS)

AF:

0.0279

AC:

144

AN:

5170

South Asian (SAS)

AF:

0.105

AC:

508

AN:

4824

European-Finnish (FIN)

AF:

0.00141

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.0272

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0104

AC:

707

AN:

68038

Other (OTH)

AF:

0.0246

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

187

373

560

746

933

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

138

184

230

<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:

0.0184

Hom.:

Bravo

AF:

0.0265

Asia WGS

AF:

0.0800

AC:

278

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.75

CADD

Benign

(source)

DANN

Benign

0.92

PhyloP100

2.8

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over