3-121770592-TAA-TA

Variant names:

• chr3-121770592-TA-T
• rs148949254
• NM_001023570.4:c.1568-19delT

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_001023570.4(IQCB1):​c.1568-19delT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.147 in 1,588,292 control chromosomes in the GnomAD database, including 18,906 homozygotes. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.11 (1287 hom., cov: 31)
  • Exomes 𝑓: 0.15 (17619 hom.)
• Consequence: IQCB1 NM_001023570.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.718
• 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: Benign. The variant received -16 ACMG points.

• BP6: Variant 3-121770592-TA-T is Benign according to our data. Variant chr3-121770592-TA-T is described in ClinVar as Benign. ClinVar VariationId is 257092.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.255 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IQCB1	NM_001023570.4	c.1568-19delT		intron_variant	Intron 14 of 14	ENST00000310864.11	NP_001018864.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IQCB1	ENST00000310864.11	c.1568-19delT		intron_variant	Intron 14 of 14	1	NM_001023570.4	ENSP00000311505.6
IQCB1	ENST00000349820.10	c.1169-19delT		intron_variant	Intron 11 of 11	1		ENSP00000323756.7
IQCB1	ENST00000393650.7	n.*546-19delT		intron_variant	Intron 13 of 13	5		ENSP00000377261.3

Frequencies

GnomAD3 genomes AF: 0.114 AC: 17388 AN: 151992 Hom.: 1289 Cov.: 31

Gnomad AFR AF: 0.0285

Gnomad AMI AF: 0.112

Gnomad AMR AF: 0.111

Gnomad ASJ AF: 0.158

Gnomad EAS AF: 0.0540

Gnomad SAS AF: 0.269

Gnomad FIN AF: 0.151

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.153

Gnomad OTH AF: 0.132

GnomAD2 exomes AF: 0.143 AC: 35642 AN: 248658 AF XY: 0.154

Gnomad AFR exome AF: 0.0225

Gnomad AMR exome AF: 0.0835

Gnomad ASJ exome AF: 0.172

Gnomad EAS exome AF: 0.0514

Gnomad FIN exome AF: 0.151

Gnomad NFE exome AF: 0.154

Gnomad OTH exome AF: 0.153

GnomAD4 exome AF: 0.150 AC: 216029 AN: 1436182 Hom.: 17619 Cov.: 20 AF XY: 0.155 AC XY: 110968 AN XY: 715950

African (AFR) AF: 0.0207 AC: 686 AN: 33064

American (AMR) AF: 0.0870 AC: 3888 AN: 44698

Ashkenazi Jewish (ASJ) AF: 0.166 AC: 4314 AN: 25982

East Asian (EAS) AF: 0.0657 AC: 2600 AN: 39584

South Asian (SAS) AF: 0.265 AC: 22753 AN: 85762

European-Finnish (FIN) AF: 0.151 AC: 7571 AN: 50076

Middle Eastern (MID) AF: 0.166 AC: 954 AN: 5738

European-Non Finnish (NFE) AF: 0.151 AC: 164524 AN: 1091722

Other (OTH) AF: 0.147 AC: 8739 AN: 59556

GnomAD4 genome AF: 0.114 AC: 17376 AN: 152110 Hom.: 1287 Cov.: 31 AF XY: 0.117 AC XY: 8719 AN XY: 74342

African (AFR) AF: 0.0285 AC: 1183 AN: 41536

American (AMR) AF: 0.111 AC: 1692 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.158 AC: 548 AN: 3470

East Asian (EAS) AF: 0.0539 AC: 279 AN: 5174

South Asian (SAS) AF: 0.268 AC: 1289 AN: 4818

European-Finnish (FIN) AF: 0.151 AC: 1593 AN: 10554

Middle Eastern (MID) AF: 0.139 AC: 41 AN: 294

European-Non Finnish (NFE) AF: 0.153 AC: 10373 AN: 67964

Other (OTH) AF: 0.131 AC: 276 AN: 2108

Alfa AF: 0.143 Hom.: 310

Bravo AF: 0.102

Asia WGS AF: 0.147 AC: 512 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Nephronophthisis Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

not provided Benign:1

Jul 17, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.72
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: rs148949254; hg19: chr3-121489439;