chr3-9937570-G-C

Variant summary

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

The NM_001077415.3(CRELD1):​c.266G>C​(p.Arg89Pro) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,458,264 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R89H) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 0.0000014 ( 0 hom. )

Consequence

CRELD1
NM_001077415.3 missense

Scores

11
6
2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.48

Publications

0 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

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, 0.872

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CRELD1NM_001077415.3 linkc.266G>C p.Arg89Pro missense_variant Exon 4 of 11 ENST00000452070.6 NP_001070883.2 Q96HD1-1A0A024R2G1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CRELD1ENST00000452070.6 linkc.266G>C p.Arg89Pro missense_variant Exon 4 of 11 2 NM_001077415.3 ENSP00000393643.2 Q96HD1-1
ENSG00000288550ENST00000683484.1 linkn.*6G>C non_coding_transcript_exon_variant Exon 18 of 24 ENSP00000507040.1 A0A804HIF2
ENSG00000288550ENST00000683484.1 linkn.*6G>C 3_prime_UTR_variant Exon 18 of 24 ENSP00000507040.1 A0A804HIF2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1458264
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
725148
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
33426
American (AMR)
AF:
0.00
AC:
0
AN:
44384
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
25896
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39636
South Asian (SAS)
AF:
0.00
AC:
0
AN:
85298
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53282
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5368
European-Non Finnish (NFE)
AF:
0.00000180
AC:
2
AN:
1110732
Other (OTH)
AF:
0.00
AC:
0
AN:
60242
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.475
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
1.0
BayesDel_addAF
Pathogenic
0.28
D
BayesDel_noAF
Pathogenic
0.16
CADD
Pathogenic
33
DANN
Uncertain
1.0
DEOGEN2
Benign
0.22
T;T;T;.
Eigen
Pathogenic
0.88
Eigen_PC
Pathogenic
0.83
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.93
.;.;D;D
M_CAP
Uncertain
0.13
D
MetaRNN
Pathogenic
0.87
D;D;D;D
MetaSVM
Uncertain
-0.26
T
MutationAssessor
Uncertain
2.7
M;M;M;M
PhyloP100
6.5
PrimateAI
Uncertain
0.71
T
PROVEAN
Pathogenic
-6.8
D;D;D;D
REVEL
Pathogenic
0.73
Sift
Pathogenic
0.0
D;D;D;D
Sift4G
Pathogenic
0.0
D;D;D;D
Polyphen
1.0
D;D;D;D
Vest4
0.98
MutPred
0.62
Gain of glycosylation at S86 (P = 0.0108);Gain of glycosylation at S86 (P = 0.0108);Gain of glycosylation at S86 (P = 0.0108);Gain of glycosylation at S86 (P = 0.0108);
MVP
0.77
MPC
0.82
ClinPred
1.0
D
GERP RS
5.2
Varity_R
0.94
gMVP
0.99
Mutation Taster
=43/57
disease causing

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.22
Details are displayed if max score is > 0.2
DS_AL_spliceai
0.22
Position offset: -8

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

Publications

Other links and lift over

dbSNP: rs760693953; hg19: chr3-9979254; API