dbSNP rs748476213: CRELD1:p.Arg383Lys (chr3-9944001-G-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The ENST00000326434.9(CRELD1):c.1148G>A(p.Arg383Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000122 in 819,922 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/19 in silico tools predict a benign 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. R383T) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000012 ( 0 hom. )

Consequence

CRELD1
ENST00000326434.9 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.769

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 links:

ENSG00000288550 (HGNC:):

ENSG00000288550 links:

PRRT3 (HGNC:26591): (proline rich transmembrane protein 3) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

PRRT3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.041222125).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CRELD1	NM_001077415.3 link	c.1049-364G>A		intron_variant	Intron 10 of 10	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.1049-364G>A		intron_variant	Intron 10 of 10	2	NM_001077415.3	ENSP00000393643.2		Q96HD1-1
ENSG00000288550	ENST00000683484.1 link	n.*697-364G>A		intron_variant	Intron 23 of 23			ENSP00000507040.1		A0A804HIF2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000122

AC:

AN:

819922

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

433504

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

21270

American (AMR)

AF:

0.00

AC:

AN:

43926

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22184

East Asian (EAS)

AF:

0.00

AC:

AN:

36784

South Asian (SAS)

AF:

0.00

AC:

AN:

73594

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53200

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4522

European-Non Finnish (NFE)

AF:

0.00000190

AC:

AN:

525172

Other (OTH)

AF:

0.00

AC:

AN:

39270

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.725

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.51

CADD

Benign

(source)

DANN

Benign

0.97

Eigen

Benign

-0.87

Eigen_PC

Benign

-0.94

FATHMM_MKL

Benign

0.069

LIST_S2

Benign

0.34

M_CAP

Benign

0.022

MetaRNN

Benign

0.041

MetaSVM

Benign

-1.0

PhyloP100

-0.77

PrimateAI

Benign

0.27

PROVEAN

Benign

0.60

REVEL

Benign

0.078

Sift

Benign

1.0

Sift4G

Benign

0.10

Polyphen

0.0

Vest4

0.21

MutPred

0.42

Gain of ubiquitination at R383 (P = 0.0155);

MVP

0.35

MPC

0.21

ClinPred

0.23

GERP RS

1.6

gMVP

0.55

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over