Genetic Variant CIROP:p.Arg191Gly (chr14-23103707-G-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001354640.2(CIROP):c.571C>G(p.Arg191Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000182 in 550,648 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 6/9 in silico tools predict 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 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.741

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.1401853).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CIROP	NM_001354640.2 link	c.571C>G	p.Arg191Gly	missense_variant	Exon 4 of 16	ENST00000637218.2	NP_001341569.1
CIROP	NM_001402427.1 link	c.580C>G	p.Arg194Gly	missense_variant	Exon 4 of 14		NP_001389356.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CIROP	ENST00000637218.2 link	c.571C>G	p.Arg191Gly	missense_variant	Exon 4 of 16	5	NM_001354640.2	ENSP00000489869.1	A0A1B0GTW7-1
CIROP	ENST00000644000.1 link	c.571C>G	p.Arg191Gly	missense_variant	Exon 4 of 14			ENSP00000493582.1	A0A1B0GTW7-2
CIROP	ENST00000642668.1 link	c.496C>G	p.Arg166Gly	missense_variant	Exon 4 of 13			ENSP00000495729.1	A0A2R8Y752
CIROP	ENST00000644147.1 link	n.628C>G		non_coding_transcript_exon_variant	Exon 4 of 9

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000182

AC:

AN:

550648

Hom.:

Cov.:

AF XY:

0.00000335

AC XY:

AN XY:

298096

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

15804

American (AMR)

AF:

0.00

AC:

AN:

34710

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

20028

East Asian (EAS)

AF:

0.00

AC:

AN:

32102

South Asian (SAS)

AF:

0.00

AC:

AN:

62764

European-Finnish (FIN)

AF:

0.00

AC:

AN:

33620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4076

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

316938

Other (OTH)

AF:

0.0000327

AC:

AN:

30606

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.24

BayesDel_noAF

Benign

-0.81

CADD

Benign

5.2

(source)

DANN

Benign

0.49

FATHMM_MKL

Benign

0.27

LIST_S2

Benign

0.48

T;T;T

MetaRNN

Benign

0.14

T;T;T

PhyloP100

0.74

GERP RS

1.5

Varity_R

0.14

gMVP

0.40

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

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

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