3-9934872-G-A

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_001077415.3(CRELD1):c.212G>A(p.Gly71Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,460,890 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

CRELD1
NM_001077415.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.23

Publications

1 publications found

Variant links:

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]

CRELD1 Gene-Disease associations (from GenCC):

complex neurodevelopmental disorder
Inheritance: AR Classification: STRONG Submitted by: Ambry Genetics
atrioventricular septal defect, susceptibility to, 2
Inheritance: AD Classification: MODERATE, LIMITED Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae), G2P
Jeffries-Lakhani neurodevelopmental syndrome
Inheritance: AR Classification: MODERATE Submitted by: G2P
congenital heart disease
Inheritance: AD Classification: LIMITED Submitted by: ClinGen

CRELD1 links:

ENSG00000288550 (HGNC:):

ENSG00000288550 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.88

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CRELD1	NM_001077415.3 link	c.212G>A	p.Gly71Glu	missense_variant	Exon 3 of 11	ENST00000452070.6	NP_001070883.2	Q96HD1-1A0A024R2G1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CRELD1	ENST00000452070.6 link	c.212G>A	p.Gly71Glu	missense_variant	Exon 3 of 11	2	NM_001077415.3	ENSP00000393643.2		Q96HD1-1
ENSG00000288550	ENST00000683484.1 link	n.1437G>A		non_coding_transcript_exon_variant	Exon 17 of 24			ENSP00000507040.1		A0A804HIF2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000401

AC:

AN:

249414

AF XY:

0.00000741

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000291

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1460890

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

726608

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33462

American (AMR)

AF:

0.0000224

AC:

AN:

44592

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26110

East Asian (EAS)

AF:

0.00

AC:

AN:

39690

South Asian (SAS)

AF:

0.00

AC:

AN:

86032

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53234

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5736

European-Non Finnish (NFE)

AF:

9.00e-7

AC:

AN:

1111668

Other (OTH)

AF:

0.00

AC:

AN:

60366

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.600

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Feb 05, 2025

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.212G>A (p.G71E) alteration is located in exon 2 (coding exon 2) of the CRELD1 gene. This alteration results from a G to A substitution at nucleotide position 212, causing the glycine (G) at amino acid position 71 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.95

BayesDel_addAF

Uncertain

0.10

BayesDel_noAF

Uncertain

-0.010

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.065

T;T;T;.

Eigen

Pathogenic

0.79

Eigen_PC

Pathogenic

0.75

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.97

.;.;D;D

M_CAP

Uncertain

0.16

MetaRNN

Pathogenic

0.88

D;D;D;D

MetaSVM

Benign

-0.60

MutationAssessor

Uncertain

2.6

M;M;M;M

PhyloP100

9.2

PrimateAI

Pathogenic

0.89

PROVEAN

Pathogenic

-7.7

D;D;D;D

REVEL

Uncertain

0.62

Sift

Pathogenic

0.0

D;D;D;D

Sift4G

Pathogenic

0.0

D;D;D;D

Polyphen

1.0

D;D;D;D

Vest4

0.87

MutPred

0.60

Gain of glycosylation at T73 (P = 0.0513);Gain of glycosylation at T73 (P = 0.0513);Gain of glycosylation at T73 (P = 0.0513);Gain of glycosylation at T73 (P = 0.0513);

MVP

0.57

MPC

0.77

ClinPred

1.0

GERP RS

4.7

PromoterAI

0.0020

Neutral

(source)

Varity_R

0.92

gMVP

0.94

Mutation Taster

=47/53

disease causing

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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3-9934872-G-A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over