NM_001023570.4:c.394-15_394-10dupATCTTT

Variant names:

• chr3-121809018-A-AAAAGAT
• rs768572151
• NM_001023570.4:c.394-15_394-10dupATCTTT

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP6 BS2

The NM_001023570.4(IQCB1):​c.394-15_394-10dupATCTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000684 in 1,534,004 control chromosomes in the GnomAD database, including 2 homozygotes. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: 𝑓 0.000099 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000065 (2 hom.)
• Consequence: IQCB1 NM_001023570.4 intron
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:1
• Conservation: PhyloP100: 1.43
• 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 -5 ACMG points.

• BP6: Variant 3-121809018-A-AAAAGAT is Benign according to our data. Variant chr3-121809018-A-AAAAGAT is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 238216.
• BS2: High Homozygotes in GnomAdExome4 at 2 AD,AR gene

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.394-15_394-10dupATCTTT		intron	N/A	NP_001018864.2
	IQCB1	NM_001319107.2		c.394-15_394-10dupATCTTT		intron	N/A	NP_001306036.1
	IQCB1	NM_001023571.4		c.394-15_394-10dupATCTTT		intron	N/A	NP_001018865.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IQCB1	ENST00000310864.11	TSL:1 MANE Select	c.394-10_394-9insATCTTT		intron	N/A	ENSP00000311505.6
	IQCB1	ENST00000349820.10	TSL:1	c.394-10_394-9insATCTTT		intron	N/A	ENSP00000323756.7
	IQCB1	ENST00000923631.1		c.466-10_466-9insATCTTT		intron	N/A	ENSP00000593690.1

Frequencies

GnomAD3 genomes AF: 0.0000989 AC: 15 AN: 151718 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000984

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000323 AC: 80 AN: 247750 AF XY: 0.000231

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00229

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000333

GnomAD4 exome AF: 0.0000651 AC: 90 AN: 1382170 Hom.: 2 Cov.: 22 AF XY: 0.0000448 AC XY: 31 AN XY: 692172

African (AFR) AF: 0.00 AC: 0 AN: 31770

American (AMR) AF: 0.00201 AC: 89 AN: 44344

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25582

East Asian (EAS) AF: 0.00 AC: 0 AN: 39170

South Asian (SAS) AF: 0.00 AC: 0 AN: 84212

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53318

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5604

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1040480

Other (OTH) AF: 0.0000173 AC: 1 AN: 57690

GnomAD4 genome AF: 0.0000988 AC: 15 AN: 151834 Hom.: 0 Cov.: 32 AF XY: 0.000121 AC XY: 9 AN XY: 74242

African (AFR) AF: 0.00 AC: 0 AN: 41506

American (AMR) AF: 0.000983 AC: 15 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3460

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.00 AC: 0 AN: 4816

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10514

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67762

Other (OTH) AF: 0.00 AC: 0 AN: 2110

Alfa AF: 0.000142 Hom.: 0

Bravo AF: 0.000215

ClinVar

ClinVar submissions as Germline

Significance: Conflicting classifications of pathogenicity

Revision: criteria provided, conflicting classifications

Pathogenic	VUS	Benign	Condition
-	-	1	Nephronophthisis (1)
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.4
Mutation Taster		=99/1	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs768572151; hg19: chr3-121527865;