3-121781772-G-C

Variant names:

• chr3-121781772-G-C
• rs121918244
• NM_001023570.4:c.1381C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.27
• Publications: 0 publications found

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

ACMG classification

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).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IQCB1	NM_001023570.4	c.1381C>G	p.Arg461Gly	missense_variant	Exon 13 of 15	ENST00000310864.11	NP_001018864.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IQCB1	ENST00000310864.11	c.1381C>G	p.Arg461Gly	missense_variant	Exon 13 of 15	1	NM_001023570.4	ENSP00000311505.6
IQCB1	ENST00000349820.10	c.982C>G	p.Arg328Gly	missense_variant	Exon 10 of 12	1		ENSP00000323756.7
IQCB1	ENST00000393650.7	n.*359C>G		non_coding_transcript_exon_variant	Exon 12 of 14	5		ENSP00000377261.3
IQCB1	ENST00000393650.7	n.*359C>G		3_prime_UTR_variant	Exon 12 of 14	5		ENSP00000377261.3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.097
BayesDel_addAF	Benign	-0.0035	T
BayesDel_noAF	Benign	-0.24
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.31	T;.
Eigen	Benign	-0.18
Eigen_PC	Benign	0.0038
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Benign	0.44	T;T
M_CAP	Benign	0.050	D
MetaRNN	Benign	0.22	T;T
MetaSVM	Benign	-0.78	T
MutationAssessor	Benign	1.4	L;.
PhyloP100		2.3
PrimateAI	Benign	0.28	T
PROVEAN	Uncertain	-2.8	D;D
REVEL	Benign	0.28
Sift	Benign	0.080	T;T
Sift4G	Uncertain	0.046	D;D
Polyphen		0.011	B;B
Vest4		0.16
MutPred		0.47		Gain of loop (P = 0.002);.;
MVP		0.92
MPC		0.11
ClinPred		0.91	D
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

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

Other links and lift over

dbSNP: rs121918244; hg19: chr3-121500619;