14-23100669-A-G

Variant names:

• chr14-23100669-A-G
• rs187174627
• NM_001354640.2:c.1992T>C

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_001354640.2(CIROP):​c.1992T>C​(p.His664His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000405 in 246,826 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: CIROP NM_001354640.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.41
• Publications: 0 publications found

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]

C14orf119 (HGNC:20270): (chromosome 14 open reading frame 119) Located in cytosol and mitochondrion. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.54).
• BP7: Synonymous conserved (PhyloP=1.41 with no splicing effect.

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.1992T>C	p.His664His	synonymous	Exon 15 of 16	NP_001341569.1	A0A1B0GTW7-1
	CIROP	NM_001402427.1		c.1827T>C	p.His609His	synonymous	Exon 13 of 14	NP_001389356.1
	C14orf119	NM_017924.4	MANE Select	c.*2588A>G		downstream_gene	N/A	NP_060394.1	Q9NWQ9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CIROP	ENST00000637218.2	TSL:5 MANE Select	c.1992T>C	p.His664His	synonymous	Exon 15 of 16	ENSP00000489869.1	A0A1B0GTW7-1
	CIROP	ENST00000644000.1		c.1818T>C	p.His606His	synonymous	Exon 13 of 14	ENSP00000493582.1	A0A1B0GTW7-2
	CIROP	ENST00000642668.1		c.1470T>C	p.His490His	synonymous	Exon 12 of 13	ENSP00000495729.1	A0A2R8Y752

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000405 AC: 1 AN: 246826 Hom.: 0 Cov.: 0 AF XY: 0.00000799 AC XY: 1 AN XY: 125106

African (AFR) AF: 0.00 AC: 0 AN: 7180

American (AMR) AF: 0.00 AC: 0 AN: 7434

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 9240

East Asian (EAS) AF: 0.0000437 AC: 1 AN: 22894

South Asian (SAS) AF: 0.00 AC: 0 AN: 3032

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 21338

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 158040

Other (OTH) AF: 0.00 AC: 0 AN: 16374

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	5.7
DANN	Benign	0.73
PhyloP100		1.4

Splicing

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

Other links and lift over

dbSNP: rs187174627; hg19: chr14-23569878;