rs150555123
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2
The NM_001369268.1(ACAN):c.7189G>A(p.Val2397Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00117 in 1,613,546 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 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_001369268.1 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Benign. Variant got -13 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ACAN | NM_001369268.1 | c.7189G>A | p.Val2397Ile | missense_variant | 15/19 | ENST00000560601.4 | NP_001356197.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ACAN | ENST00000560601.4 | c.7189G>A | p.Val2397Ile | missense_variant | 15/19 | 3 | NM_001369268.1 | ENSP00000453581.2 |
Frequencies
GnomAD3 genomes AF: 0.000880 AC: 134AN: 152212Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000740 AC: 183AN: 247260Hom.: 1 AF XY: 0.000714 AC XY: 96AN XY: 134486
GnomAD4 exome AF: 0.00120 AC: 1758AN: 1461218Hom.: 1 Cov.: 31 AF XY: 0.00117 AC XY: 852AN XY: 726884
GnomAD4 genome AF: 0.000880 AC: 134AN: 152328Hom.: 0 Cov.: 32 AF XY: 0.000779 AC XY: 58AN XY: 74484
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:3
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 24, 2024 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics | Apr 27, 2017 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Aug 31, 2017 | - - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jan 01, 2024 | ACAN: BP4 - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 12, 2021 | The c.7075G>A (p.V2359I) alteration is located in exon 14 (coding exon 13) of the ACAN gene. This alteration results from a G to A substitution at nucleotide position 7075, causing the valine (V) at amino acid position 2359 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | May 04, 2023 | Variant summary: ACAN c.7189G>A (p.Val2397Ile) results in a conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00074 in 247260 control chromosomes in the gnomAD database, including 1 homozygote. The observed variant frequency is approximately 1184 fold of the estimated maximal expected allele frequency for a pathogenic variant in ACAN causing ACAN-Related Disorders phenotype (6.3e-07), strongly suggesting that the variant is benign. To our knowledge, no occurrence of c.7189G>A in individuals affected with ACAN-Related Disorders and no experimental evidence demonstrating its impact on protein function have been reported. Four ClinVar submitters (evaluation after 2014) cite this variant as uncertain significance (n=2) and likely benign (n=2). Based on the evidence outlined above, the variant was classified as likely benign. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at