Genetic Variant CIROP:p.Pro13del (chr14-23104882-TGGC-T) – ACMG Classification: Likely_benign (-3 pts)

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 1P and 4B. PM4_SupportingBS1

The NM_001354640.2(CIROP):c.36_38delGCC(p.Pro13del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000144 in 661,488 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00014 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00014 ( 0 hom. )

Consequence

CIROP
NM_001354640.2 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.83

Publications

0 publications found

Variant links:

Genes affected

CIROP (HGNC:53647): (ciliated left-right organizer metallopeptidase) Predicted to enable peptidase activity. Predicted to be involved in cell adhesion and proteolysis. Predicted to be integral component of membrane. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

CIROP links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -3 ACMG points.

PM4

Nonframeshift variant in NON repetitive region in NM_001354640.2. Strenght limited to Supporting due to length of the change: 1aa.

BS1

Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.00014 (16/114302) while in subpopulation SAS AF = 0.00499 (14/2804). AF 95% confidence interval is 0.00302. There are 0 homozygotes in GnomAd4. There are 13 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001354640.2. 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
	CIROP	NM_001354640.2	MANE Select	c.36_38delGCC	p.Pro13del	disruptive_inframe_deletion	Exon 1 of 16	NP_001341569.1	A0A1B0GTW7-1
	CIROP	NM_001402427.1		c.36_38delGCC	p.Pro13del	disruptive_inframe_deletion	Exon 1 of 14	NP_001389356.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CIROP	ENST00000637218.2	TSL:5 MANE Select	c.36_38delGCC	p.Pro13del	disruptive_inframe_deletion	Exon 1 of 16	ENSP00000489869.1	A0A1B0GTW7-1
CIROP	ENST00000644000.1		c.36_38delGCC	p.Pro13del	disruptive_inframe_deletion	Exon 1 of 14	ENSP00000493582.1	A0A1B0GTW7-2
CIROP	ENST00000940842.1		c.36_38delGCC	p.Pro13del	disruptive_inframe_deletion	Exon 1 of 12	ENSP00000610901.1

Frequencies

GnomAD3 genomes

AF:

0.000140

AC:

AN:

114190

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000104

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00499

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000203

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000378

AC:

AN:

79442

AF XY:

0.000541

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000802

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000144

AC:

AN:

547186

Hom.:

AF XY:

0.000233

AC XY:

AN XY:

296078

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

15602

American (AMR)

AF:

0.00

AC:

AN:

34440

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19742

East Asian (EAS)

AF:

0.00

AC:

AN:

32088

South Asian (SAS)

AF:

0.00122

AC:

AN:

62190

European-Finnish (FIN)

AF:

0.00

AC:

AN:

33684

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4032

European-Non Finnish (NFE)

AF:

0.00000635

AC:

AN:

314984

Other (OTH)

AF:

0.0000329

AC:

AN:

30424

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.000140

AC:

AN:

114302

Hom.:

Cov.:

AF XY:

0.000238

AC XY:

AN XY:

54702

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

37490

American (AMR)

AF:

0.000103

AC:

AN:

9666

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2682

East Asian (EAS)

AF:

0.00

AC:

AN:

3800

South Asian (SAS)

AF:

0.00499

AC:

AN:

2804

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6260

Middle Eastern (MID)

AF:

0.00

AC:

AN:

250

European-Non Finnish (NFE)

AF:

0.0000203

AC:

AN:

49280

Other (OTH)

AF:

0.00

AC:

AN:

1498

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.522

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00

Hom.:

Asia WGS

AF:

0.000289

AC:

AN:

3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

1.8

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over