rs12492214

Positions:

• chr3-121799150-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001023570.4(IQCB1):​c.766+46T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.105 in 1,457,066 control chromosomes in the GnomAD database, including 8,554 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.10 (851 hom., cov: 31)
  • Exomes 𝑓: 0.11 (7703 hom.)
• Consequence: IQCB1 NM_001023570.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.491

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP6: Variant 3-121799150-A-G is Benign according to our data. Variant chr3-121799150-A-G is described in ClinVar as [Benign]. Clinvar id is 257094.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.145 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IQCB1	NM_001023570.4	c.766+46T>C		intron_variant		ENST00000310864.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IQCB1	ENST00000310864.11	c.766+46T>C		intron_variant		1	NM_001023570.4	P1

Frequencies

GnomAD3 genomes AF: 0.103 AC: 15628 AN: 151582 Hom.: 851 Cov.: 31

Gnomad AFR AF: 0.106

Gnomad AMI AF: 0.0658

Gnomad AMR AF: 0.0716

Gnomad ASJ AF: 0.107

Gnomad EAS AF: 0.0720

Gnomad SAS AF: 0.154

Gnomad FIN AF: 0.133

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.103

Gnomad OTH AF: 0.104

GnomAD3 exomes AF: 0.102 AC: 24035 AN: 235088 Hom.: 1381 AF XY: 0.107 AC XY: 13626 AN XY: 127866

Gnomad AFR exome AF: 0.109

Gnomad AMR exome AF: 0.0488

Gnomad ASJ exome AF: 0.104

Gnomad EAS exome AF: 0.0606

Gnomad SAS exome AF: 0.161

Gnomad FIN exome AF: 0.133

Gnomad NFE exome AF: 0.102

Gnomad OTH exome AF: 0.110

GnomAD4 exome AF: 0.106 AC: 137889 AN: 1305366 Hom.: 7703 Cov.: 18 AF XY: 0.108 AC XY: 70865 AN XY: 656666

Gnomad4 AFR exome AF: 0.103

Gnomad4 AMR exome AF: 0.0497

Gnomad4 ASJ exome AF: 0.109

Gnomad4 EAS exome AF: 0.0751

Gnomad4 SAS exome AF: 0.159

Gnomad4 FIN exome AF: 0.135

Gnomad4 NFE exome AF: 0.103

Gnomad4 OTH exome AF: 0.106

GnomAD4 genome AF: 0.103 AC: 15626 AN: 151700 Hom.: 851 Cov.: 31 AF XY: 0.104 AC XY: 7738 AN XY: 74154

Gnomad4 AFR AF: 0.105

Gnomad4 AMR AF: 0.0715

Gnomad4 ASJ AF: 0.107

Gnomad4 EAS AF: 0.0714

Gnomad4 SAS AF: 0.154

Gnomad4 FIN AF: 0.133

Gnomad4 NFE AF: 0.103

Gnomad4 OTH AF: 0.108

Alfa AF: 0.105 Hom.: 157

Bravo AF: 0.0935

Asia WGS AF: 0.135 AC: 467 AN: 3470

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Sep 13, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	13
DANN	Benign	0.83

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

Other links and lift over

dbSNP: rs12492214; hg19: chr3-121517997;