Variant 16-85107898-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_198491.3(CIBAR2):c.374T>G(p.Leu125Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000791 in 1,614,128 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00056 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00081 ( 3 hom. )

Consequence

CIBAR2
NM_198491.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.01

Variant links:

Genes affected

CIBAR2 (HGNC:24781): (CBY1 interacting BAR domain containing 2) Predicted to be involved in cilium assembly. Predicted to be located in centriole and cytoplasm. Predicted to be active in ciliary basal body and ciliary transition zone. [provided by Alliance of Genome Resources, Apr 2022]

CIBAR2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.25624275).

BS2

High Homozygotes in GnomAdExome4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CIBAR2	NM_198491.3 link	c.374T>G	p.Leu125Arg	missense_variant	Exon 4 of 9	ENST00000539556.6	NP_940893.1	Q6ZTR7A0A1X7SC74
CIBAR2	NM_001366920.1 link	c.374T>G	p.Leu125Arg	missense_variant	Exon 4 of 9		NP_001353849.1
CIBAR2	XM_011523063.2 link	c.374T>G	p.Leu125Arg	missense_variant	Exon 4 of 10		XP_011521365.1	Q6ZTR7A0A1X7SC74
CIBAR2	XM_017023198.2 link	c.374T>G	p.Leu125Arg	missense_variant	Exon 4 of 10		XP_016878687.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CIBAR2	ENST00000539556.6 link	c.374T>G	p.Leu125Arg	missense_variant	Exon 4 of 9	5	NM_198491.3	ENSP00000443411.1		A0A1X7SC74
CIBAR2	ENST00000618669.3 link	c.89T>G	p.Leu30Arg	missense_variant	Exon 2 of 7	5		ENSP00000478373.1		A0A087WU51

Frequencies

GnomAD3 genomes

AF:

0.000559

AC:

AN:

152174

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000966

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:

0.00113

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000525

AC:

132

AN:

251490

Hom.:

AF XY:

0.000530

AC XY:

AN XY:

135922

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.000145

Gnomad ASJ exome

AF:

0.000198

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.00104

Gnomad OTH exome

AF:

0.000651

GnomAD4 exome

AF:

0.000815

AC:

1191

AN:

1461836

Hom.:

Cov.:

AF XY:

0.000835

AC XY:

607

AN XY:

727218

show subpopulations

Gnomad4 AFR exome

AF:

0.000179

Gnomad4 AMR exome

AF:

0.000179

Gnomad4 ASJ exome

AF:

0.000191

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000812

Gnomad4 FIN exome

AF:

0.000131

Gnomad4 NFE exome

AF:

0.000987

Gnomad4 OTH exome

AF:

0.000994

GnomAD4 genome

AF:

0.000558

AC:

AN:

152292

Hom.:

Cov.:

AF XY:

0.000376

AC XY:

AN XY:

74460

show subpopulations

Gnomad4 AFR

AF:

0.0000963

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:

0.00113

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000883

Hom.:

Bravo

AF:

0.000559

TwinsUK

AF:

0.00108

AC:

ALSPAC

AF:

0.00104

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00128

AC:

ExAC

AF:

0.000544

AC:

EpiCase

AF:

0.00109

EpiControl

AF:

0.00113

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jul 02, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.374T>G (p.L125R) alteration is located in exon 4 (coding exon 4) of the FAM92B gene. This alteration results from a T to G substitution at nucleotide position 374, causing the leucine (L) at amino acid position 125 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.27

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0073

.;T

Eigen

Benign

0.13

Eigen_PC

Uncertain

0.23

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.86

D;D

M_CAP

Benign

0.042

MetaRNN

Benign

0.26

T;T

MetaSVM

Benign

-0.83

MutationAssessor

Uncertain

2.4

.;M

PrimateAI

Uncertain

0.55

PROVEAN

Benign

-1.8

N;.

REVEL

Benign

0.23

Sift

Benign

0.33

T;.

Sift4G

Benign

0.22

T;D

Polyphen

0.53

.;P

Vest4

0.67

MVP

0.58

MPC

0.094

ClinPred

0.042

GERP RS

5.7

Varity_R

0.40

gMVP

0.51

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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