14-23104857-G-T

Variant names:

• chr14-23104857-G-T
• rs185661693
• NM_001354640.2:c.64C>A

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.64C>A​(p.Arg22Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000182 in 549,906 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: 0.0000018 (0 hom.)
• Consequence: CIROP NM_001354640.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.461
• 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]

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=-0.62).
• BP7: Synonymous conserved (PhyloP=0.461 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.64C>A	p.Arg22Arg	synonymous	Exon 1 of 16	NP_001341569.1	A0A1B0GTW7-1
	CIROP	NM_001402427.1		c.64C>A	p.Arg22Arg	synonymous	Exon 1 of 14	NP_001389356.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CIROP	ENST00000637218.2	TSL:5 MANE Select	c.64C>A	p.Arg22Arg	synonymous	Exon 1 of 16	ENSP00000489869.1	A0A1B0GTW7-1
	CIROP	ENST00000644000.1		c.64C>A	p.Arg22Arg	synonymous	Exon 1 of 14	ENSP00000493582.1	A0A1B0GTW7-2
	CIROP	ENST00000940842.1		c.64C>A	p.Arg22Arg	synonymous	Exon 1 of 12	ENSP00000610901.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000182 AC: 1 AN: 549906 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 297608

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 15796

American (AMR) AF: 0.00 AC: 0 AN: 34644

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19950

East Asian (EAS) AF: 0.00 AC: 0 AN: 32096

South Asian (SAS) AF: 0.00 AC: 0 AN: 62658

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33796

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4068

European-Non Finnish (NFE) AF: 0.00000316 AC: 1 AN: 316316

Other (OTH) AF: 0.00 AC: 0 AN: 30582

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	5.2
DANN	Benign	0.73
PhyloP100		0.46
PromoterAI		-0.0019	Neutral

Splicing

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

Other links and lift over

dbSNP: rs185661693; hg19: chr14-23574066;