3-9941024-C-T
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_001077415.3(CRELD1):c.635C>T(p.Ser212Leu) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.0000855 in 1,614,016 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. S212S) has been classified as Likely benign.
Frequency
Consequence
NM_001077415.3 missense, splice_region
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CRELD1 | NM_001077415.3 | c.635C>T | p.Ser212Leu | missense_variant, splice_region_variant | 6/11 | ENST00000452070.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CRELD1 | ENST00000452070.6 | c.635C>T | p.Ser212Leu | missense_variant, splice_region_variant | 6/11 | 2 | NM_001077415.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000105 AC: 16AN: 152136Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.0000955 AC: 24AN: 251354Hom.: 0 AF XY: 0.000110 AC XY: 15AN XY: 135870
GnomAD4 exome AF: 0.0000835 AC: 122AN: 1461880Hom.: 0 Cov.: 33 AF XY: 0.000105 AC XY: 76AN XY: 727240
GnomAD4 genome ? AF: 0.000105 AC: 16AN: 152136Hom.: 0 Cov.: 31 AF XY: 0.000108 AC XY: 8AN XY: 74318
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 28, 2023 | The c.635C>T (p.S212L) alteration is located in exon 5 (coding exon 5) of the CRELD1 gene. This alteration results from a C to T substitution at nucleotide position 635, causing the serine (S) at amino acid position 212 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Atrioventricular septal defect, susceptibility to, 2 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Dec 23, 2022 | 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. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The leucine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. ClinVar contains an entry for this variant (Variation ID: 647903). This variant has not been reported in the literature in individuals affected with CRELD1-related conditions. This variant is present in population databases (rs138336691, gnomAD 0.02%). This sequence change replaces serine, which is neutral and polar, with leucine, which is neutral and non-polar, at codon 212 of the CRELD1 protein (p.Ser212Leu). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at