Genetic Variant CIROP:p.Pro13dup (chr14-23104882-T-TGGC) – ACMG Classification: Benign (-9 pts)

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 1P and 10B. PM4_SupportingBP6_ModerateBS1BS2

The NM_001354640.2(CIROP):c.36_38dupGCC(p.Pro13dup) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0012 in 661,488 control chromosomes in the GnomAD database, including 3 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0014 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0012 ( 3 hom. )

Consequence

CIROP
NM_001354640.2 disruptive_inframe_insertion

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0680

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: Benign. The variant received -9 ACMG points.

PM4

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

BP6

Variant 14-23104882-T-TGGC is Benign according to our data. Variant chr14-23104882-T-TGGC is described in ClinVar as [Likely_benign]. Clinvar id is 2644090.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0014 (160/114302) while in subpopulation NFE AF = 0.0026 (128/49280). AF 95% confidence interval is 0.00223. There are 0 homozygotes in GnomAd4. There are 65 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position FAILED quality control check.

BS2

High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CIROP	NM_001354640.2 link	c.36_38dupGCC	p.Pro13dup	disruptive_inframe_insertion	Exon 1 of 16	ENST00000637218.2	NP_001341569.1
CIROP	NM_001402427.1 link	c.36_38dupGCC	p.Pro13dup	disruptive_inframe_insertion	Exon 1 of 14		NP_001389356.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CIROP	ENST00000637218.2 link	c.36_38dupGCC	p.Pro13dup	disruptive_inframe_insertion	Exon 1 of 16	5	NM_001354640.2	ENSP00000489869.1	A0A1B0GTW7-1
CIROP	ENST00000644000.1 link	c.36_38dupGCC	p.Pro13dup	disruptive_inframe_insertion	Exon 1 of 14			ENSP00000493582.1	A0A1B0GTW7-2
CIROP	ENST00000644147.1 link	n.84_86dupGCC		non_coding_transcript_exon_variant	Exon 1 of 9
CIROP	ENST00000642668.1 link	c.-40_-38dupGCC		upstream_gene_variant				ENSP00000495729.1	A0A2R8Y752

Frequencies

GnomAD3 genomes

AF:

0.00141

AC:

161

AN:

114190

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000375

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00145

Gnomad ASJ

AF:

0.000746

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000160

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00262

Gnomad OTH

AF:

0.000678

GnomAD2 exomes

AF:

0.00175

AC:

139

AN:

79442

AF XY:

0.00167

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000642

Gnomad ASJ exome

AF:

0.000743

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00384

Gnomad OTH exome

AF:

0.00479

GnomAD4 exome

AF:

0.00115

AC:

631

AN:

547186

Hom.:

Cov.:

AF XY:

0.00112

AC XY:

333

AN XY:

296078

show subpopulations

Gnomad4 AFR exome

AF:

0.0000641

AC:

AN:

15602

Gnomad4 AMR exome

AF:

0.000407

AC:

AN:

34440

Gnomad4 ASJ exome

AF:

0.000507

AC:

AN:

19742

Gnomad4 EAS exome

AF:

0.00

AC:

AN:

32088

Gnomad4 SAS exome

AF:

0.00

AC:

AN:

62190

Gnomad4 FIN exome

AF:

0.00

AC:

AN:

33684

Gnomad4 NFE exome

AF:

0.00181

AC:

570

AN:

314982

Gnomad4 Remaining exome

AF:

0.00115

AC:

AN:

30426

Heterozygous variant carriers

108

135

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

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:

0.00140

AC:

160

AN:

114302

Hom.:

Cov.:

AF XY:

0.00119

AC XY:

AN XY:

54702

show subpopulations

Gnomad4 AFR

AF:

0.000373

AC:

0.000373433

AN:

0.000373433

Gnomad4 AMR

AF:

0.00145

AC:

0.00144838

AN:

0.00144838

Gnomad4 ASJ

AF:

0.000746

AC:

0.000745712

AN:

0.000745712

Gnomad4 EAS

AF:

0.00

AC:

AN:

Gnomad4 SAS

AF:

0.00

AC:

AN:

Gnomad4 FIN

AF:

0.000160

AC:

0.000159744

AN:

0.000159744

Gnomad4 NFE

AF:

0.00260

AC:

0.0025974

AN:

0.0025974

Gnomad4 OTH

AF:

0.000668

AC:

0.000667557

AN:

0.000667557

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

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:

0.000893

Hom.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jul 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

CIROP: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over