Variant 14-23102120-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 2P and 9B. PM2BP4_ModerateBP6_ModerateBP7BS1

The NM_001354640.2(CIROP):c.1281C>T(p.Ser427Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000384 in 702,984 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0011 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00017 ( 0 hom. )

Consequence

CIROP
NM_001354640.2 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.512

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=-0.32).

BP6

Variant 14-23102120-G-A is Benign according to our data. Variant chr14-23102120-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2644088.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.512 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00115 (175/152186) while in subpopulation AFR AF= 0.00409 (170/41516). AF 95% confidence interval is 0.00359. There are 1 homozygotes in gnomad4. There are 94 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CIROP	NM_001354640.2 link	c.1281C>T	p.Ser427Ser	synonymous_variant	Exon 10 of 16	ENST00000637218.2	NP_001341569.1
CIROP	NM_001402427.1 link	c.1116C>T	p.Ser372Ser	synonymous_variant	Exon 8 of 14		NP_001389356.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CIROP	ENST00000637218.2 link	c.1281C>T	p.Ser427Ser	synonymous_variant	Exon 10 of 16	5	NM_001354640.2	ENSP00000489869.1	A0A1B0GTW7-1
CIROP	ENST00000644000.1 link	c.1107C>T	p.Ser369Ser	synonymous_variant	Exon 8 of 14			ENSP00000493582.1	A0A1B0GTW7-2
CIROP	ENST00000642668.1 link	c.1032C>T	p.Ser344Ser	synonymous_variant	Exon 8 of 13			ENSP00000495729.1	A0A2R8Y752
CIROP	ENST00000644147.1 link	n.1038C>T		non_coding_transcript_exon_variant	Exon 7 of 9

Frequencies

GnomAD3 genomes

AF:

0.00112

AC:

171

AN:

152068

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00401

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:

0.00

Gnomad OTH

AF:

0.000956

GnomAD3 exomes

AF:

0.000223

AC:

AN:

134656

Hom.:

AF XY:

0.000191

AC XY:

AN XY:

73268

show subpopulations

Gnomad AFR exome

AF:

0.00294

Gnomad AMR exome

AF:

0.000245

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000445

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000189

Gnomad OTH exome

AF:

0.000724

GnomAD4 exome

AF:

0.000172

AC:

AN:

550798

Hom.:

Cov.:

AF XY:

0.000134

AC XY:

AN XY:

298174

show subpopulations

Gnomad4 AFR exome

AF:

0.00310

Gnomad4 AMR exome

AF:

0.000317

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000311

Gnomad4 SAS exome

AF:

0.0000319

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000315

Gnomad4 OTH exome

AF:

0.000490

GnomAD4 genome

AF:

0.00115

AC:

175

AN:

152186

Hom.:

Cov.:

AF XY:

0.00126

AC XY:

AN XY:

74402

show subpopulations

Gnomad4 AFR

AF:

0.00409

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:

0.00

Gnomad4 OTH

AF:

0.000946

Alfa

AF:

0.0000428

Hom.:

Bravo

AF:

0.00116

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jun 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

CIROP: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.32

CADD

Benign

0.43

DANN

Benign

0.82

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over