rs200158965
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_001023570.4(IQCB1):āc.1046A>Gā(p.Lys349Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000248 in 1,613,610 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ā ).
Frequency
Consequence
NM_001023570.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
IQCB1 | NM_001023570.4 | c.1046A>G | p.Lys349Arg | missense_variant | 11/15 | ENST00000310864.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
IQCB1 | ENST00000310864.11 | c.1046A>G | p.Lys349Arg | missense_variant | 11/15 | 1 | NM_001023570.4 | P1 | |
IQCB1 | ENST00000349820.10 | c.647A>G | p.Lys216Arg | missense_variant | 8/12 | 1 | |||
IQCB1 | ENST00000393650.7 | c.*24A>G | 3_prime_UTR_variant, NMD_transcript_variant | 10/14 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.0000263 AC: 4AN: 152190Hom.: 0 Cov.: 32
GnomAD4 exome AF: 0.0000246 AC: 36AN: 1461302Hom.: 0 Cov.: 30 AF XY: 0.0000220 AC XY: 16AN XY: 726976
GnomAD4 genome ? AF: 0.0000263 AC: 4AN: 152308Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74468
ClinVar
Submissions by phenotype
Senior-Loken syndrome 5 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | May 17, 2022 | - - |
Nephronophthisis Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 06, 2022 | This sequence change replaces lysine, which is basic and polar, with arginine, which is basic and polar, at codon 349 of the IQCB1 protein (p.Lys349Arg). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with IQCB1-related conditions. ClinVar contains an entry for this variant (Variation ID: 216488). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The arginine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at