chr3-121810164-T-C

Variant names:

• chr3-121810164-T-C
• rs7623901
• NM_001023570.4:c.394-1155A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 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):

• ciliopathy

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• Senior-Loken syndrome 5

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• 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 -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001023570.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IQCB1	NM_001023570.4	MANE Select	c.394-1155A>G		intron	N/A	NP_001018864.2	Q15051-1
	IQCB1	NM_001319107.2		c.394-1155A>G		intron	N/A	NP_001306036.1	Q15051-1
	IQCB1	NM_001023571.4		c.394-1155A>G		intron	N/A	NP_001018865.2	Q15051-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IQCB1	ENST00000310864.11	TSL:1 MANE Select	c.394-1155A>G		intron	N/A	ENSP00000311505.6	Q15051-1
	IQCB1	ENST00000349820.10	TSL:1	c.394-1155A>G		intron	N/A	ENSP00000323756.7	Q15051-2
	IQCB1	ENST00000923631.1		c.466-1155A>G		intron	N/A	ENSP00000593690.1

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

African (AFR) AF: 0.914 AC: 37927 AN: 41512

American (AMR) AF: 0.825 AC: 12589 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.721 AC: 2503 AN: 3470

East Asian (EAS) AF: 0.945 AC: 4894 AN: 5180

South Asian (SAS) AF: 0.857 AC: 4128 AN: 4816

European-Finnish (FIN) AF: 0.766 AC: 8067 AN: 10538

Middle Eastern (MID) AF: 0.694 AC: 204 AN: 294

European-Non Finnish (NFE) AF: 0.763 AC: 51830 AN: 67890

Other (OTH) AF: 0.785 AC: 1652 AN: 2104

Alfa AF: 0.799 Hom.: 17623

Bravo AF: 0.825

Asia WGS AF: 0.906 AC: 3146 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	6.1
DANN	Benign	0.29
PhyloP100		-0.18
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: rs7623901; hg19: chr3-121529011;