Genetic Variant IQCB1:p.Leu192Val (chr3-121807357-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_001023570.4(IQCB1):c.574C>G(p.Leu192Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. L192L) has been classified as Benign.

Frequency

Genomes: not found (cov: 30)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

IQCB1
NM_001023570.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.76

Publications

29 publications found

Variant links:

Genes affected

IQCB1 (HGNC:28949): (IQ motif containing B1) This gene encodes a nephrocystin protein that interacts with calmodulin and the retinitis pigmentosa GTPase regulator protein. The encoded protein has a central coiled-coil region and two calmodulin-binding IQ domains. It is localized to the primary cilia of renal epithelial cells and connecting cilia of photoreceptor cells. The protein is thought to play a role in ciliary function. Defects in this gene result in Senior-Loken syndrome type 5. Alternative splicing results in multiple transcript variants. A pseudogene of this gene is found on chromosome 6. [provided by RefSeq, Jan 2016]

IQCB1 Gene-Disease associations (from GenCC):

Senior-Loken syndrome 5
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
Leber congenital amaurosis
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
Senior-Loken syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

IQCB1 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=0.165696).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IQCB1	NM_001023570.4 link	c.574C>G	p.Leu192Val	missense_variant	Exon 7 of 15	ENST00000310864.11	NP_001018864.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IQCB1	ENST00000310864.11 link	c.574C>G	p.Leu192Val	missense_variant	Exon 7 of 15	1	NM_001023570.4	ENSP00000311505.6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1361826

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

683186

African (AFR)

AF:

0.00

AC:

AN:

31390

American (AMR)

AF:

0.00

AC:

AN:

44468

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25418

East Asian (EAS)

AF:

0.00

AC:

AN:

39144

South Asian (SAS)

AF:

0.00

AC:

AN:

84222

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53290

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5570

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1021368

Other (OTH)

AF:

0.00

AC:

AN:

56956

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.39

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.038

T;.;.;T

Eigen

Benign

0.17

Eigen_PC

Benign

0.17

FATHMM_MKL

Uncertain

0.79

LIST_S2

Benign

0.79

T;T;T;T

M_CAP

Benign

0.0071

MetaRNN

Benign

0.17

T;T;T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

1.4

L;L;.;.

PhyloP100

1.8

PrimateAI

Uncertain

0.52

PROVEAN

Benign

-1.0

N;N;N;N

REVEL

Benign

0.10

Sift

Benign

0.23

T;T;T;T

Sift4G

Uncertain

0.022

D;D;.;.

Vest4

0.42

ClinPred

0.61

GERP RS

3.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.064

gMVP

0.21

Mutation Taster

=86/14

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

Details are displayed if max score is > 0.2

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

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over