rs1920320

Variant names:

• chr3-121828680-A-C
• rs1920320
• NM_001023570.4:c.101-48T>G

Your query was ambiguous. Multiple possible variants found:

• chr3-121828680-A-C
• chr3-121828680-A-G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001023570.4(IQCB1):​c.101-48T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000851 in 1,175,088 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 8.5e-7 (0 hom.)
• Consequence: IQCB1 NM_001023570.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.66
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IQCB1	NM_001023570.4	MANE Select	c.101-48T>G		intron	N/A	NP_001018864.2
	IQCB1	NM_001319107.2		c.101-48T>G		intron	N/A	NP_001306036.1
	IQCB1	NM_001023571.4		c.101-48T>G		intron	N/A	NP_001018865.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IQCB1	ENST00000310864.11	TSL:1 MANE Select	c.101-48T>G		intron	N/A	ENSP00000311505.6
	IQCB1	ENST00000349820.10	TSL:1	c.101-48T>G		intron	N/A	ENSP00000323756.7
	IQCB1	ENST00000923631.1		c.101-48T>G		intron	N/A	ENSP00000593690.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 8.51e-7 AC: 1 AN: 1175088 Hom.: 0 Cov.: 16 AF XY: 0.00000168 AC XY: 1 AN XY: 595404

African (AFR) AF: 0.00 AC: 0 AN: 27138

American (AMR) AF: 0.00 AC: 0 AN: 40182

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24010

East Asian (EAS) AF: 0.00 AC: 0 AN: 37676

South Asian (SAS) AF: 0.00 AC: 0 AN: 76460

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51800

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3940

European-Non Finnish (NFE) AF: 0.00000116 AC: 1 AN: 863592

Other (OTH) AF: 0.00 AC: 0 AN: 50290

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	14
DANN	Benign	0.66
PhyloP100		1.7

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: rs1920320; hg19: chr3-121547527;