CRELD1

cysteine rich with EGF like domains 1

Basic information

Region (hg38): 3:9933793-9945413

Previous symbols: [ "AVSD2" ]

Links

ENSG00000163703 ∙ NCBI:78987 ∙ OMIM:607170 ∙ HGNC:14630 ∙ Uniprot:Q96HD1 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• atrioventricular septal defect, susceptibility to, 2 (Moderate), mode of inheritance: AD
• atrioventricular septal defect, susceptibility to, 2 (Strong), mode of inheritance: AD
• atrioventricular septal defect, susceptibility to, 2 (Limited), mode of inheritance: AD
• congenital heart disease (Limited), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Atrioventricular septal defect, partial, with or without heterotaxy; Jeffries-Lakhani neurodevelopmental syndrome	AD/AR	Allergy/Immunology/Infectious; Cardiovascular	Atrioventricular septal defect, partial, with or without heterotaxy can involve congenital cardiac anomalies, and awareness may allow early management; Jeffries-Lakhani neurodevelopmental syndrome can involve recurrent infections and cardiovascular anomalies, including cardiac arrhythmias requiring defribillator placement, as well as cardiac malformations in some individuals, and awareness can allow early and aggressive treatment of infections as well as identification and management of cardiovascular manifestations	Allergy/Immunology/Infectious; Cardiovascular; Craniofacial; Gastrointestinal; Neurologic; Ophthalmologic	12632326; 15857420; 21080147; 22740159; 3794718

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CRELD1 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CRELD1 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			1	22	6	29
missense			55	6	4	65
nonsense			4			4
start loss						0
frameshift		3	6			9
inframe indel			1			1
splice donor/acceptor (+/-2bp)			1			1
splice region			2	5	2	9
non coding			2	8	14	24
Total	0	3	70	36	24

Variants in CRELD1

This is a list of pathogenic ClinVar variants found in the CRELD1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
3-9933888-C-T			Benign (May 11, 2021)
3-9934176-T-C			Benign (May 17, 2021)
3-9934334-G-T			Benign (Nov 12, 2018)
3-9934446-C-T		CRELD1-related disorder	Uncertain significance (May 29, 2024)
3-9934471-A-G			Likely benign (Dec 03, 2018)
3-9934475-A-G		Atrioventricular septal defect, susceptibility to, 2	Benign (Feb 01, 2024)
3-9934475-A-A		not specified • Atrioventricular septal defect, susceptibility to, 2	Benign (Jan 14, 2024)
3-9934485-G-A		Inborn genetic diseases	Uncertain significance (Dec 20, 2021)
3-9934504-C-T		Atrioventricular septal defect, susceptibility to, 2	Likely benign (Jul 25, 2022)
3-9934518-T-G		Atrioventricular septal defect, susceptibility to, 2	Uncertain significance (Jun 13, 2022)
3-9934531-C-T		Atrioventricular septal defect, susceptibility to, 2	Benign (Dec 20, 2023)
3-9934533-C-T		Atrioventricular septal defect, susceptibility to, 2 • Inborn genetic diseases	Uncertain significance (Apr 29, 2024)
3-9934553-C-T		Inborn genetic diseases	Uncertain significance (Dec 12, 2023)
3-9934557-C-G		Inborn genetic diseases	Uncertain significance (Mar 14, 2023)
3-9934557-C-T		Inborn genetic diseases	Uncertain significance (Oct 29, 2021)
3-9934574-T-G			Uncertain significance (Dec 06, 2019)
3-9934617-G-A			Uncertain significance (Dec 14, 2023)
3-9934623-C-T		Atrioventricular septal defect, susceptibility to, 2	Likely benign (Dec 21, 2023)
3-9934816-A-G		Atrioventricular septal defect, susceptibility to, 2	Likely benign (Apr 11, 2021)
3-9934875-A-G		Atrioventricular septal defect, susceptibility to, 2	Uncertain significance (Jan 08, 2023)
3-9934883-T-C		Congenital heart defects, multiple types, 4	Pathogenic (-)
3-9934892-G-C			Uncertain significance (Jan 11, 2022)
3-9934894-G-T		Atrioventricular septal defect, susceptibility to, 2	Uncertain significance (Jun 19, 2023)
3-9934911-AAGAC-A			Likely pathogenic (Nov 30, 2018)
3-9934927-T-G		Atrioventricular septal defect, susceptibility to, 2	Benign (Aug 24, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CRELD1	protein_coding	protein_coding	ENST00000326434	11	11592

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.34e-11	0.539	125590	0	158	125748	0.000628

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.175	235	243	0.968	0.0000143	2740
Missense in Polyphen		84	92.424	0.90885		1018
Synonymous	-1.48	111	92.8	1.20	0.00000573	798
Loss of Function	1.36	21	28.9	0.727	0.00000182	298

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00125	0.00125
Ashkenazi Jewish	0.00	0.00
East Asian	0.000218	0.000217
Finnish	0.00	0.00
European (Non-Finnish)	0.000995	0.000994
Middle Eastern	0.000218	0.000217
South Asian	0.000197	0.000196
Other	0.000326	0.000326

dbNSFP

Source: dbNSFP

• Disease: DISEASE: Atrioventricular septal defect 2 (AVSD2) [MIM:606217]: A congenital heart malformation characterized by a common atrioventricular junction coexisting with deficient atrioventricular septation. The complete form involves underdevelopment of the lower part of the atrial septum and the upper part of the ventricular septum; the valve itself is also shared. A less severe form, known as ostium primum atrial septal defect, is characterized by separate atrioventricular valvar orifices despite a common junction. {ECO:0000269|PubMed:12632326, ECO:0000269|PubMed:15857420}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.

Recessive Scores

• pRec: 0.0922

Intolerance Scores

• loftool: 0.424
• rvis_EVS: 0.38
• rvis_percentile_EVS: 75.51

Haploinsufficiency Scores

• pHI: 0.0920
• hipred: N
• hipred_score: 0.169
• ghis: 0.468

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.402

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Creld1
• Phenotype: cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); embryo phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); cellular phenotype; craniofacial phenotype

Gene ontology

• Biological process: endocardial cushion development;cardiac septum development
• Cellular component: integral component of membrane;collagen-containing extracellular matrix
• Molecular function: extracellular matrix structural constituent;calcium ion binding