chr3-9941000-G-A
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Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2
The NM_001077415.3(CRELD1):c.611G>A(p.Arg204His) variant causes a missense change. The variant allele was found at a frequency of 0.00000867 in 1,614,048 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 Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 31)
Exomes 𝑓: 0.0000089 ( 0 hom. )
Consequence
CRELD1
NM_001077415.3 missense
NM_001077415.3 missense
Scores
2
8
9
Clinical Significance
Conservation
PhyloP100: 6.49
Genes affected
CRELD1 (HGNC:14630): (cysteine rich with EGF like domains 1) This gene encodes a member of a subfamily of epidermal growth factor-related proteins. The encoded protein is characterized by a cysteine-rich with epidermal growth factor-like domain. This protein may function as a cell adhesion molecule. Mutations in this gene are the cause of atrioventricular septal defect. Alternate splicing results in multiple transcript variants.[provided by RefSeq, Apr 2010]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -5 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.3963544).
BS2
High AC in GnomAdExome4 at 13 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CRELD1 | NM_001077415.3 | c.611G>A | p.Arg204His | missense_variant | 6/11 | ENST00000452070.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CRELD1 | ENST00000452070.6 | c.611G>A | p.Arg204His | missense_variant | 6/11 | 2 | NM_001077415.3 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152166Hom.: 0 Cov.: 31
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GnomAD3 exomes AF: 0.00000796 AC: 2AN: 251362Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135880
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GnomAD4 exome AF: 0.00000889 AC: 13AN: 1461882Hom.: 0 Cov.: 33 AF XY: 0.00000413 AC XY: 3AN XY: 727242
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GnomAD4 genome AF: 0.00000657 AC: 1AN: 152166Hom.: 0 Cov.: 31 AF XY: 0.0000134 AC XY: 1AN XY: 74352
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Atrioventricular septal defect, susceptibility to, 2 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Oct 24, 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 are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals affected with CRELD1-related conditions. This variant is present in population databases (rs760277160, gnomAD 0.007%). This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 204 of the CRELD1 protein (p.Arg204His). - |
Computational scores
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Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Pathogenic
DANN
Pathogenic
DEOGEN2
Benign
T;T;T;.
Eigen
Uncertain
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
.;.;D;D
M_CAP
Benign
D
MetaRNN
Benign
T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;M;M;M
MutationTaster
Benign
D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;D;D;D
REVEL
Benign
Sift
Uncertain
D;D;D;D
Sift4G
Uncertain
D;D;D;D
Polyphen
D;D;D;D
Vest4
MutPred
Gain of catalytic residue at N205 (P = 0.0478);Gain of catalytic residue at N205 (P = 0.0478);Gain of catalytic residue at N205 (P = 0.0478);Gain of catalytic residue at N205 (P = 0.0478);
MVP
MPC
0.31
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at