chr14-23104882-T-TGGC

Variant summary

Our verdict is Benign. Variant got -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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
BS2
High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CIROPNM_001354640.2 linkc.36_38dupGCC p.Pro13dup disruptive_inframe_insertion Exon 1 of 16 ENST00000637218.2 NP_001341569.1
CIROPNM_001402427.1 linkc.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 Appris UniProt
CIROPENST00000637218.2 linkc.36_38dupGCC p.Pro13dup disruptive_inframe_insertion Exon 1 of 16 5 NM_001354640.2 ENSP00000489869.1 A0A1B0GTW7-1
CIROPENST00000644000.1 linkc.36_38dupGCC p.Pro13dup disruptive_inframe_insertion Exon 1 of 14 ENSP00000493582.1 A0A1B0GTW7-2
CIROPENST00000644147.1 linkn.84_86dupGCC non_coding_transcript_exon_variant Exon 1 of 9
CIROPENST00000642668.1 linkc.-40_-38dupGCC upstream_gene_variant ENSP00000495729.1 A0A2R8Y752

Frequencies

GnomAD3 genomes
AF:
0.00141
AC:
161
AN:
114190
Hom.:
0
Cov.:
31
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
GnomAD3 exomes
AF:
0.00175
AC:
139
AN:
79442
Hom.:
22
AF XY:
0.00167
AC XY:
74
AN XY:
44342
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 SAS 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.:
3
Cov.:
0
AF XY:
0.00112
AC XY:
333
AN XY:
296078
show subpopulations
Gnomad4 AFR exome
AF:
0.0000641
Gnomad4 AMR exome
AF:
0.000407
Gnomad4 ASJ exome
AF:
0.000507
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00181
Gnomad4 OTH exome
AF:
0.00115
GnomAD4 genome
AF:
0.00140
AC:
160
AN:
114302
Hom.:
0
Cov.:
31
AF XY:
0.00119
AC XY:
65
AN XY:
54702
show subpopulations
Gnomad4 AFR
AF:
0.000373
Gnomad4 AMR
AF:
0.00145
Gnomad4 ASJ
AF:
0.000746
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.000160
Gnomad4 NFE
AF:
0.00260
Gnomad4 OTH
AF:
0.000668

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingCeGaT Center for Human Genetics TuebingenJul 01, 2023CIROP: 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.

Other links and lift over

dbSNP: rs751420164; hg19: chr14-23574091; API