chr14-23104882-T-TGGC

Variant names:

• chr14-23104882-T-TGGC
• rs751420164
• NM_001354640.2:c.36_38dupGCC

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 1P and 10B. PM4_Supporting BP6_Moderate BS1 BS2

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
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0680

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]

ACMG classification

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
CIROP	NM_001354640.2	c.36_38dupGCC	p.Pro13dup	disruptive_inframe_insertion	Exon 1 of 16	ENST00000637218.2	NP_001341569.1
CIROP	NM_001402427.1	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	Appris	UniProt
CIROP	ENST00000637218.2	c.36_38dupGCC	p.Pro13dup	disruptive_inframe_insertion	Exon 1 of 16	5	NM_001354640.2	ENSP00000489869.1
CIROP	ENST00000644000.1	c.36_38dupGCC	p.Pro13dup	disruptive_inframe_insertion	Exon 1 of 14			ENSP00000493582.1
CIROP	ENST00000644147.1	n.84_86dupGCC		non_coding_transcript_exon_variant	Exon 1 of 9
CIROP	ENST00000642668.1	c.-40_-38dupGCC		upstream_gene_variant				ENSP00000495729.1

Frequencies

GnomAD3 genomes AF: 0.00141 AC: 161 AN: 114190 Hom.: 0 Cov.: 31

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

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

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

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

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs751420164; hg19: chr14-23574091;