3-121781725-G-A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 2P and 12B. PM2BP4_StrongBP6_Very_Strong

The NM_001023570.4(IQCB1):​c.1410+18C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000344 in 1,455,176 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: not found (cov: 31)
Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

IQCB1
NM_001023570.4 intron

Scores

2

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.0160

Publications

0 publications found
Variant links:
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

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.85).
BP6
Variant 3-121781725-G-A is Benign according to our data. Variant chr3-121781725-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 257091.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
IQCB1NM_001023570.4 linkc.1410+18C>T intron_variant Intron 13 of 14 ENST00000310864.11 NP_001018864.2 Q15051-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
IQCB1ENST00000310864.11 linkc.1410+18C>T intron_variant Intron 13 of 14 1 NM_001023570.4 ENSP00000311505.6 Q15051-1
IQCB1ENST00000349820.10 linkc.1011+18C>T intron_variant Intron 10 of 11 1 ENSP00000323756.7 Q15051-2
IQCB1ENST00000393650.7 linkn.*388+18C>T intron_variant Intron 12 of 13 5 ENSP00000377261.3 Q15051-3

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
AF:
0.00000344
AC:
5
AN:
1455176
Hom.:
0
Cov.:
31
AF XY:
0.00000414
AC XY:
3
AN XY:
724230
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
33324
American (AMR)
AF:
0.00
AC:
0
AN:
44642
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26016
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39562
South Asian (SAS)
AF:
0.0000349
AC:
3
AN:
86006
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53218
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5746
European-Non Finnish (NFE)
AF:
0.00000181
AC:
2
AN:
1106578
Other (OTH)
AF:
0.00
AC:
0
AN:
60084
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.515
Heterozygous variant carriers
0
1
1
2
2
3
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
Cov.:
31
Alfa
AF:
0.0000936
Hom.:
0
Bravo
AF:
0.00000378

ClinVar

Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not specified Benign:1
-
PreventionGenetics, part of Exact Sciences
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Nephronophthisis Benign:1
May 25, 2024
Labcorp Genetics (formerly Invitae), Labcorp
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.85
CADD
Benign
3.9
DANN
Benign
0.55
PhyloP100
-0.016

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

Publications

Other links and lift over

dbSNP: rs886038375; hg19: chr3-121500572; API