chr3-9937549-C-A
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_001077415.3(CRELD1):c.258-13C>A variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00218 in 1,593,490 control chromosomes in the GnomAD database, including 66 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0022 ( 12 hom., cov: 32)
Exomes 𝑓: 0.0022 ( 54 hom. )
Consequence
CRELD1
NM_001077415.3 splice_polypyrimidine_tract, intron
NM_001077415.3 splice_polypyrimidine_tract, intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.0540
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 Benign. Variant got -20 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.83).
BP6
Variant 3-9937549-C-A is Benign according to our data. Variant chr3-9937549-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 1605652.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00223 (340/152210) while in subpopulation EAS AF= 0.0507 (262/5170). AF 95% confidence interval is 0.0456. There are 12 homozygotes in gnomad4. There are 194 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High AC in GnomAd4 at 340 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CRELD1 | NM_001077415.3 | c.258-13C>A | splice_polypyrimidine_tract_variant, intron_variant | ENST00000452070.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CRELD1 | ENST00000452070.6 | c.258-13C>A | splice_polypyrimidine_tract_variant, intron_variant | 2 | NM_001077415.3 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00224 AC: 340AN: 152092Hom.: 12 Cov.: 32
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GnomAD3 exomes AF: 0.00478 AC: 1145AN: 239292Hom.: 19 AF XY: 0.00464 AC XY: 599AN XY: 129030
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GnomAD4 exome AF: 0.00217 AC: 3134AN: 1441280Hom.: 54 Cov.: 29 AF XY: 0.00227 AC XY: 1631AN XY: 717162
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GnomAD4 genome AF: 0.00223 AC: 340AN: 152210Hom.: 12 Cov.: 32 AF XY: 0.00261 AC XY: 194AN XY: 74400
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Atrioventricular septal defect, susceptibility to, 2 Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Sep 17, 2021 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 28, 2024 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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