NM_001023570.4:c.101-48T>C

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001023570.4(IQCB1):​c.101-48T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.259 in 1,325,464 control chromosomes in the GnomAD database, including 47,486 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.25 (4959 hom., cov: 32)
  • Exomes 𝑓: 0.26 (42527 hom.)
• Consequence: IQCB1 NM_001023570.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 1.66
• Publications: 7 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: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 3-121828680-A-G is Benign according to our data. Variant chr3-121828680-A-G is described in ClinVar as Benign. ClinVar VariationId is 257089.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.277 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.101-48T>C		intron	N/A	NP_001018864.2
	IQCB1	NM_001319107.2		c.101-48T>C		intron	N/A	NP_001306036.1
	IQCB1	NM_001023571.4		c.101-48T>C		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.101-48T>C		intron	N/A	ENSP00000311505.6
	IQCB1	ENST00000349820.10	TSL:1	c.101-48T>C		intron	N/A	ENSP00000323756.7
	IQCB1	ENST00000923631.1		c.101-48T>C		intron	N/A	ENSP00000593690.1

Frequencies

GnomAD3 genomes AF: 0.246 AC: 37465 AN: 151996 Hom.: 4958 Cov.: 32

Gnomad AFR AF: 0.256

Gnomad AMI AF: 0.396

Gnomad AMR AF: 0.151

Gnomad ASJ AF: 0.222

Gnomad EAS AF: 0.0799

Gnomad SAS AF: 0.0981

Gnomad FIN AF: 0.281

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.280

Gnomad OTH AF: 0.229

GnomAD2 exomes AF: 0.218 AC: 45803 AN: 209938 AF XY: 0.216

Gnomad AFR exome AF: 0.258

Gnomad AMR exome AF: 0.123

Gnomad ASJ exome AF: 0.219

Gnomad EAS exome AF: 0.0810

Gnomad FIN exome AF: 0.288

Gnomad NFE exome AF: 0.285

Gnomad OTH exome AF: 0.220

GnomAD4 exome AF: 0.260 AC: 305469 AN: 1173350 Hom.: 42527 Cov.: 16 AF XY: 0.254 AC XY: 151222 AN XY: 594562

African (AFR) AF: 0.260 AC: 7041 AN: 27108

American (AMR) AF: 0.129 AC: 5199 AN: 40160

Ashkenazi Jewish (ASJ) AF: 0.215 AC: 5160 AN: 23990

East Asian (EAS) AF: 0.0891 AC: 3358 AN: 37670

South Asian (SAS) AF: 0.110 AC: 8384 AN: 76432

European-Finnish (FIN) AF: 0.284 AC: 14689 AN: 51780

Middle Eastern (MID) AF: 0.163 AC: 642 AN: 3940

European-Non Finnish (NFE) AF: 0.289 AC: 248985 AN: 862040

Other (OTH) AF: 0.239 AC: 12011 AN: 50230

GnomAD4 genome AF: 0.246 AC: 37476 AN: 152114 Hom.: 4959 Cov.: 32 AF XY: 0.239 AC XY: 17744 AN XY: 74366

African (AFR) AF: 0.255 AC: 10588 AN: 41490

American (AMR) AF: 0.150 AC: 2299 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.222 AC: 772 AN: 3470

East Asian (EAS) AF: 0.0799 AC: 414 AN: 5184

South Asian (SAS) AF: 0.0981 AC: 474 AN: 4830

European-Finnish (FIN) AF: 0.281 AC: 2970 AN: 10572

Middle Eastern (MID) AF: 0.204 AC: 60 AN: 294

European-Non Finnish (NFE) AF: 0.280 AC: 19057 AN: 67964

Other (OTH) AF: 0.228 AC: 481 AN: 2114

Alfa AF: 0.248 Hom.: 911

Bravo AF: 0.242

Asia WGS AF: 0.116 AC: 408 AN: 3474

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	14
DANN	Benign	0.71
PhyloP100		1.7
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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;