rs1135750

Variant names:

• chr3-121770148-C-G
• rs1135750
• NM_001023570.4:c.*197G>C

Your query was ambiguous. Multiple possible variants found:

• chr3-121770148-C-G
• chr3-121770148-C-T

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.*197G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.619 in 563,820 control chromosomes in the GnomAD database, including 110,383 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.64 (31987 hom., cov: 32)
  • Exomes 𝑓: 0.61 (78396 hom.)
• Consequence: IQCB1 NM_001023570.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.162
• Publications: 16 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 3-121770148-C-G is Benign according to our data. Variant chr3-121770148-C-G is described in ClinVar as Benign. ClinVar VariationId is 342768.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.708 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.*197G>C		3_prime_UTR	Exon 15 of 15	NP_001018864.2	Q15051-1
	IQCB1	NM_001319107.2		c.*197G>C		3_prime_UTR	Exon 15 of 15	NP_001306036.1	Q15051-1
	IQCB1	NM_001023571.4		c.*197G>C		3_prime_UTR	Exon 12 of 12	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.*197G>C		3_prime_UTR	Exon 15 of 15	ENSP00000311505.6	Q15051-1
	IQCB1	ENST00000349820.10	TSL:1	c.*197G>C		3_prime_UTR	Exon 12 of 12	ENSP00000323756.7	Q15051-2
	IQCB1	ENST00000923631.1		c.*197G>C		3_prime_UTR	Exon 16 of 16	ENSP00000593690.1

Frequencies

GnomAD3 genomes AF: 0.644 AC: 97819 AN: 151922 Hom.: 31955 Cov.: 32

Gnomad AFR AF: 0.715

Gnomad AMI AF: 0.680

Gnomad AMR AF: 0.664

Gnomad ASJ AF: 0.554

Gnomad EAS AF: 0.319

Gnomad SAS AF: 0.660

Gnomad FIN AF: 0.663

Gnomad MID AF: 0.554

Gnomad NFE AF: 0.622

Gnomad OTH AF: 0.631

GnomAD4 exome AF: 0.610 AC: 251056 AN: 411780 Hom.: 78396 Cov.: 3 AF XY: 0.611 AC XY: 132507 AN XY: 217012

African (AFR) AF: 0.714 AC: 8390 AN: 11744

American (AMR) AF: 0.716 AC: 12643 AN: 17662

Ashkenazi Jewish (ASJ) AF: 0.561 AC: 7173 AN: 12786

East Asian (EAS) AF: 0.323 AC: 9283 AN: 28714

South Asian (SAS) AF: 0.655 AC: 27930 AN: 42620

European-Finnish (FIN) AF: 0.668 AC: 16635 AN: 24916

Middle Eastern (MID) AF: 0.518 AC: 939 AN: 1814

European-Non Finnish (NFE) AF: 0.620 AC: 153577 AN: 247586

Other (OTH) AF: 0.605 AC: 14486 AN: 23938

GnomAD4 genome AF: 0.644 AC: 97902 AN: 152040 Hom.: 31987 Cov.: 32 AF XY: 0.645 AC XY: 47951 AN XY: 74330

African (AFR) AF: 0.715 AC: 29638 AN: 41478

American (AMR) AF: 0.665 AC: 10156 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.554 AC: 1919 AN: 3466

East Asian (EAS) AF: 0.319 AC: 1652 AN: 5178

South Asian (SAS) AF: 0.659 AC: 3176 AN: 4822

European-Finnish (FIN) AF: 0.663 AC: 6993 AN: 10554

Middle Eastern (MID) AF: 0.544 AC: 160 AN: 294

European-Non Finnish (NFE) AF: 0.622 AC: 42265 AN: 67958

Other (OTH) AF: 0.630 AC: 1326 AN: 2106

Alfa AF: 0.503 Hom.: 1332

Bravo AF: 0.641

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Senior-Loken syndrome 5 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.2
DANN	Benign	0.37
PhyloP100		0.16
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: rs1135750; hg19: chr3-121488995; COSMIC: COSV60436121;