Genetic Variant IQCB1:p.Arg461Gly (chr3-121781772-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.1381C>G(p.Arg461Gly) 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. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R461Q) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 31)

Consequence

IQCB1
NM_001023570.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.27

Publications

0 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):

ciliopathy
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
Senior-Loken syndrome 5
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
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=0.2191152).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001023570.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
IQCB1	NM_001023570.4	MANE Select	c.1381C>G	p.Arg461Gly	missense	Exon 13 of 15	NP_001018864.2	Q15051-1
IQCB1	NM_001319107.2		c.1381C>G	p.Arg461Gly	missense	Exon 13 of 15	NP_001306036.1	Q15051-1
IQCB1	NM_001023571.4		c.982C>G	p.Arg328Gly	missense	Exon 10 of 12	NP_001018865.2	Q15051-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
IQCB1	ENST00000310864.11	TSL:1 MANE Select	c.1381C>G	p.Arg461Gly	missense	Exon 13 of 15	ENSP00000311505.6	Q15051-1
IQCB1	ENST00000349820.10	TSL:1	c.982C>G	p.Arg328Gly	missense	Exon 10 of 12	ENSP00000323756.7	Q15051-2
IQCB1	ENST00000923631.1		c.1453C>G	p.Arg485Gly	missense	Exon 14 of 16	ENSP00000593690.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.097

BayesDel_addAF

Benign

-0.0035

BayesDel_noAF

Benign

-0.24

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.31

Eigen

Benign

-0.18

Eigen_PC

Benign

0.0038

FATHMM_MKL

Uncertain

0.83

LIST_S2

Benign

0.44

M_CAP

Benign

0.050

MetaRNN

Benign

0.22

MetaSVM

Benign

-0.78

MutationAssessor

Benign

1.4

PhyloP100

2.3

PrimateAI

Benign

0.28

PROVEAN

Uncertain

-2.8

REVEL

Benign

0.28

Sift

Benign

0.080

Sift4G

Uncertain

0.046

Polyphen

0.011

Vest4

0.16

MutPred

0.47

Gain of loop (P = 0.002)

MVP

0.92

MPC

0.11

ClinPred

0.91

GERP RS

4.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.14

gMVP

0.19

Mutation Taster

=68/32

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over