rs45493995
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 1P and 9B. PP2BP4_StrongBP6BS1
The NM_000875.5(IGF1R):c.2894G>A(p.Ser965Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000211 in 1,612,882 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_000875.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -8 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
IGF1R | ENST00000650285.1 | c.2894G>A | p.Ser965Asn | missense_variant | Exon 15 of 21 | NM_000875.5 | ENSP00000497069.1 | |||
IGF1R | ENST00000560972.1 | n.197G>A | non_coding_transcript_exon_variant | Exon 3 of 4 | 1 | |||||
IGF1R | ENST00000649865.1 | c.2891G>A | p.Ser964Asn | missense_variant | Exon 15 of 21 | ENSP00000496919.1 |
Frequencies
GnomAD3 genomes AF: 0.0000394 AC: 6AN: 152246Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000124 AC: 31AN: 250604Hom.: 0 AF XY: 0.0000591 AC XY: 8AN XY: 135414
GnomAD4 exome AF: 0.0000192 AC: 28AN: 1460518Hom.: 0 Cov.: 30 AF XY: 0.0000138 AC XY: 10AN XY: 726604
GnomAD4 genome AF: 0.0000394 AC: 6AN: 152364Hom.: 0 Cov.: 33 AF XY: 0.0000537 AC XY: 4AN XY: 74504
ClinVar
Submissions by phenotype
not specified Uncertain:1
Variant summary: IGF1R c.2894G>A (p.Ser965Asn) results in a conservative amino acid change in the encoded protein sequence. Four of four in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00012 in 250604 control chromosomes (gnomAD). c.2894G>A has been reported in the literature in one individual affected with neurodevelopmental disorders, microcephaly as one of the features (Wang_2023). The report does not provide unequivocal conclusions about association of the variant with Growth Delay Due To Insulin-Like Growth Factor I Resistance. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication have been ascertained in the context of this evaluation (PMID: 37501076). ClinVar contains an entry for this variant (Variation ID: 731844). Based on the evidence outlined above, the variant was classified as uncertain significance. -
Growth delay due to insulin-like growth factor I resistance Uncertain:1
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. -
not provided Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at