Genetic Variant NM_001354640.2:c.571C>A (chr14-23103707-G-T) – ACMG Classification: Benign (-7 pts)

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 2P and 9B. PM2BP4_StrongBP7BS1

The NM_001354640.2(CIROP):c.571C>A(p.Arg191Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000683 in 702,850 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: 𝑓 0.000072 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000067 ( 0 hom. )

Consequence

CIROP
NM_001354640.2 synonymous

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -7 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP7

Synonymous conserved (PhyloP=0.741 with no splicing effect.

BS1

Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.0000672 (37/550648) while in subpopulation MID AF= 0.00123 (5/4076). AF 95% confidence interval is 0.000483. There are 0 homozygotes in gnomad4_exome. There are 22 alleles in male gnomad4_exome subpopulation. Median coverage is 0. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CIROP	NM_001354640.2 link	c.571C>A	p.Arg191Arg	synonymous_variant	Exon 4 of 16	ENST00000637218.2	NP_001341569.1
CIROP	NM_001402427.1 link	c.580C>A	p.Arg194Arg	synonymous_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>A	p.Arg191Arg	synonymous_variant	Exon 4 of 16	5	NM_001354640.2	ENSP00000489869.1	A0A1B0GTW7-1
CIROP	ENST00000644000.1 link	c.571C>A	p.Arg191Arg	synonymous_variant	Exon 4 of 14			ENSP00000493582.1	A0A1B0GTW7-2
CIROP	ENST00000642668.1 link	c.496C>A	p.Arg166Arg	synonymous_variant	Exon 4 of 13			ENSP00000495729.1	A0A2R8Y752
CIROP	ENST00000644147.1 link	n.628C>A		non_coding_transcript_exon_variant	Exon 4 of 9

Frequencies

GnomAD3 genomes

AF:

0.0000723

AC:

AN:

152202

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000118

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000521

AC:

AN:

134436

Hom.:

AF XY:

0.0000683

AC XY:

AN XY:

73226

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000819

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000890

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000379

Gnomad OTH exome

AF:

0.000242

GnomAD4 exome

AF:

0.0000672

AC:

AN:

550648

Hom.:

Cov.:

AF XY:

0.0000738

AC XY:

AN XY:

298096

show subpopulations

Gnomad4 AFR exome

AF:

0.0000633

Gnomad4 AMR exome

AF:

0.0000864

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000312

Gnomad4 SAS exome

AF:

0.0000637

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000599

Gnomad4 OTH exome

AF:

0.000131

GnomAD4 genome

AF:

0.0000723

AC:

AN:

152202

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74362

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000118

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000427

Hom.:

Bravo

AF:

0.0000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

1.1

DANN

Benign

0.59

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over