3-121810164-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001023570.4(IQCB1):c.394-1155A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.819 in 151,982 control chromosomes in the GnomAD database, including 51,415 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.82 (51415 hom., cov: 31)
• Consequence: IQCB1 NM_001023570.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.181

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.923 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IQCB1	NM_001023570.4	c.394-1155A>G		intron_variant		ENST00000310864.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IQCB1	ENST00000310864.11	c.394-1155A>G		intron_variant		1	NM_001023570.4	P1

Frequencies

GnomAD3 genomes AF: 0.819 AC: 124368 AN: 151864 Hom.: 51357 Cov.: 31

Gnomad AFR AF: 0.914

Gnomad AMI AF: 0.761

Gnomad AMR AF: 0.824

Gnomad ASJ AF: 0.721

Gnomad EAS AF: 0.944

Gnomad SAS AF: 0.857

Gnomad FIN AF: 0.766

Gnomad MID AF: 0.690

Gnomad NFE AF: 0.763

Gnomad OTH AF: 0.782

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.819 AC: 124488 AN: 151982 Hom.: 51415 Cov.: 31 AF XY: 0.821 AC XY: 60966 AN XY: 74268

Gnomad4 AFR AF: 0.914

Gnomad4 AMR AF: 0.825

Gnomad4 ASJ AF: 0.721

Gnomad4 EAS AF: 0.945

Gnomad4 SAS AF: 0.857

Gnomad4 FIN AF: 0.766

Gnomad4 NFE AF: 0.763

Gnomad4 OTH AF: 0.785

Alfa AF: 0.795 Hom.: 9208

Bravo AF: 0.825

Asia WGS AF: 0.906 AC: 3146 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
Cadd	Benign	6.1
Dann	Benign	0.29

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: rs7623901; hg19: chr3-121529011;