Genetic Variant NM_001354640.2:c.36_38dupGCC (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

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: 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 VariationId 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 passed quality control check.

BS2

High Homozygotes in GnomAdExome4 at 3 AR gene

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_38dupGCC	p.Pro13dup	disruptive_inframe_insertion	Exon 1 of 16	NP_001341569.1	A0A1B0GTW7-1
	CIROP	NM_001402427.1		c.36_38dupGCC	p.Pro13dup	disruptive_inframe_insertion	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_38dupGCC	p.Pro13dup	disruptive_inframe_insertion	Exon 1 of 16	ENSP00000489869.1	A0A1B0GTW7-1
CIROP	ENST00000644000.1		c.36_38dupGCC	p.Pro13dup	disruptive_inframe_insertion	Exon 1 of 14	ENSP00000493582.1	A0A1B0GTW7-2
CIROP	ENST00000940842.1		c.36_38dupGCC	p.Pro13dup	disruptive_inframe_insertion	Exon 1 of 12	ENSP00000610901.1

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

African (AFR)

AF:

0.0000641

AC:

AN:

15602

American (AMR)

AF:

0.000407

AC:

AN:

34440

Ashkenazi Jewish (ASJ)

AF:

0.000507

AC:

AN:

19742

East Asian (EAS)

AF:

0.00

AC:

AN:

32088

South Asian (SAS)

AF:

0.00

AC:

AN:

62190

European-Finnish (FIN)

AF:

0.00

AC:

AN:

33684

Middle Eastern (MID)

AF:

0.000248

AC:

AN:

4032

European-Non Finnish (NFE)

AF:

0.00181

AC:

570

AN:

314982

Other (OTH)

AF:

0.00115

AC:

AN:

30426

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

108

135

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

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

African (AFR)

AF:

0.000373

AC:

AN:

37490

American (AMR)

AF:

0.00145

AC:

AN:

9666

Ashkenazi Jewish (ASJ)

AF:

0.000746

AC:

AN:

2682

East Asian (EAS)

AF:

0.00

AC:

AN:

3800

South Asian (SAS)

AF:

0.00

AC:

AN:

2804

European-Finnish (FIN)

AF:

0.000160

AC:

AN:

6260

Middle Eastern (MID)

AF:

0.00

AC:

AN:

250

European-Non Finnish (NFE)

AF:

0.00260

AC:

128

AN:

49280

Other (OTH)

AF:

0.000668

AC:

AN:

1498

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

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:

0.000893

Hom.:

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.068

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