3-121770592-TAA-TA

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_001023570.4(IQCB1):c.1568-19del 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

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 -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 id is 257092.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-121770592-TA-T is described in Lovd as [Benign].
• 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/exons	MANE	UniProt
IQCB1	NM_001023570.4	c.1568-19del		intron_variant		ENST00000310864.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IQCB1	ENST00000310864.11	c.1568-19del		intron_variant		1	NM_001023570.4	P1
IQCB1	ENST00000349820.10	c.1169-19del		intron_variant		1
IQCB1	ENST00000393650.7	c.*546-19del		intron_variant, NMD_transcript_variant		5

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

GnomAD3 exomes AF: 0.143 AC: 35642 AN: 248658 Hom.: 3135 AF XY: 0.154 AC XY: 20780 AN XY: 134556

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 SAS exome AF: 0.276

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

Gnomad4 AFR exome AF: 0.0207

Gnomad4 AMR exome AF: 0.0870

Gnomad4 ASJ exome AF: 0.166

Gnomad4 EAS exome AF: 0.0657

Gnomad4 SAS exome AF: 0.265

Gnomad4 FIN exome AF: 0.151

Gnomad4 NFE exome AF: 0.151

Gnomad4 OTH exome AF: 0.147

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

Gnomad4 AFR AF: 0.0285

Gnomad4 AMR AF: 0.111

Gnomad4 ASJ AF: 0.158

Gnomad4 EAS AF: 0.0539

Gnomad4 SAS AF: 0.268

Gnomad4 FIN AF: 0.151

Gnomad4 NFE AF: 0.153

Gnomad4 OTH AF: 0.131

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

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

Nephronophthisis Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 31, 2024

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 17, 2019

- -

Computational scores

Source: dbNSFP v4.3

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: rs148949254; hg19: chr3-121489439;