3-121799150-A-G

Variant names:

• chr3-121799150-A-G
• rs12492214
• NM_001023570.4:c.766+46T>C

Variant summary

Our verdict is Benign. The variant received -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:3
• Conservation: PhyloP100: 0.491
• Publications: 3 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: Benign. The variant received -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 VariationId 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 rank	MANE	Protein	UniProt
IQCB1	NM_001023570.4	c.766+46T>C		intron_variant	Intron 8 of 14	ENST00000310864.11	NP_001018864.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IQCB1	ENST00000310864.11	c.766+46T>C		intron_variant	Intron 8 of 14	1	NM_001023570.4	ENSP00000311505.6

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

GnomAD2 exomes AF: 0.102 AC: 24035 AN: 235088 AF XY: 0.107

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 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

African (AFR) AF: 0.103 AC: 3113 AN: 30120

American (AMR) AF: 0.0497 AC: 2138 AN: 43024

Ashkenazi Jewish (ASJ) AF: 0.109 AC: 2711 AN: 24856

East Asian (EAS) AF: 0.0751 AC: 2901 AN: 38638

South Asian (SAS) AF: 0.159 AC: 12901 AN: 81096

European-Finnish (FIN) AF: 0.135 AC: 7107 AN: 52710

Middle Eastern (MID) AF: 0.130 AC: 498 AN: 3840

European-Non Finnish (NFE) AF: 0.103 AC: 100712 AN: 976190

Other (OTH) AF: 0.106 AC: 5808 AN: 54892

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

African (AFR) AF: 0.105 AC: 4370 AN: 41464

American (AMR) AF: 0.0715 AC: 1087 AN: 15212

Ashkenazi Jewish (ASJ) AF: 0.107 AC: 370 AN: 3468

East Asian (EAS) AF: 0.0714 AC: 370 AN: 5184

South Asian (SAS) AF: 0.154 AC: 743 AN: 4820

European-Finnish (FIN) AF: 0.133 AC: 1405 AN: 10560

Middle Eastern (MID) AF: 0.122 AC: 36 AN: 294

European-Non Finnish (NFE) AF: 0.103 AC: 6958 AN: 67688

Other (OTH) AF: 0.108 AC: 227 AN: 2098

Alfa AF: 0.105 Hom.: 163

Bravo AF: 0.0935

Asia WGS AF: 0.135 AC: 467 AN: 3470

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Sep 13, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

not specified Benign:1

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	13
DANN	Benign	0.83
PhyloP100		0.49
Mutation Taster		=100/0	polymorphism (auto)

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: rs12492214; hg19: chr3-121517997;