ENST00000326434.9:c.1136T>C

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000326434.9(CRELD1):c.1136T>C(p.Met379Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.021 in 1,036,400 control chromosomes in the GnomAD database, including 1,683 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M379R) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.065 ( 939 hom., cov: 32)

Exomes 𝑓: 0.013 ( 744 hom. )

Consequence

CRELD1
ENST00000326434.9 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.304

Publications

8 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: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0027036965).

BP6

Variant 3-9943989-T-C is Benign according to our data. Variant chr3-9943989-T-C is described in ClinVar as Benign. ClinVar VariationId is 137031.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.212 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CRELD1	NM_001077415.3 link	c.1049-376T>C		intron_variant	Intron 10 of 10	ENST00000452070.6	NP_001070883.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CRELD1	ENST00000452070.6 link	c.1049-376T>C		intron_variant	Intron 10 of 10	2	NM_001077415.3	ENSP00000393643.2
ENSG00000288550	ENST00000683484.1 link	n.*697-376T>C		intron_variant	Intron 23 of 23			ENSP00000507040.1

Frequencies

GnomAD3 genomes

AF:

0.0650

AC:

9880

AN:

152004

Hom.:

933

Cov.:

show subpopulations

Gnomad AFR

AF:

0.215

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0291

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0241

Gnomad SAS

AF:

0.0484

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.000912

Gnomad OTH

AF:

0.0512

GnomAD2 exomes

AF:

0.0264

AC:

6568

AN:

249054

AF XY:

0.0229

show subpopulations

Gnomad AFR exome

AF:

0.224

Gnomad AMR exome

AF:

0.0303

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0253

Gnomad FIN exome

AF:

0.000139

Gnomad NFE exome

AF:

0.000925

Gnomad OTH exome

AF:

0.0121

GnomAD4 exome

AF:

0.0134

AC:

11835

AN:

884278

Hom.:

744

Cov.:

AF XY:

0.0133

AC XY:

6162

AN XY:

463528

show subpopulations

African (AFR)

AF:

0.229

AC:

5200

AN:

22680

American (AMR)

AF:

0.0312

AC:

1371

AN:

44012

Ashkenazi Jewish (ASJ)

AF:

0.0000444

AC:

AN:

22544

East Asian (EAS)

AF:

0.0208

AC:

770

AN:

37038

South Asian (SAS)

AF:

0.0406

AC:

3036

AN:

74838

European-Finnish (FIN)

AF:

0.000207

AC:

AN:

53226

Middle Eastern (MID)

AF:

0.0323

AC:

149

AN:

4614

European-Non Finnish (NFE)

AF:

0.000625

AC:

365

AN:

583780

Other (OTH)

AF:

0.0224

AC:

932

AN:

41546

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

711

1422

2133

2844

3555

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

166

332

498

664

830

<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

AF:

0.0652

AC:

9917

AN:

152122

Hom.:

939

Cov.:

AF XY:

0.0631

AC XY:

4689

AN XY:

74356

show subpopulations

African (AFR)

AF:

0.215

AC:

8932

AN:

41464

American (AMR)

AF:

0.0293

AC:

448

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.0241

AC:

125

AN:

5178

South Asian (SAS)

AF:

0.0479

AC:

231

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10582

Middle Eastern (MID)

AF:

0.0272

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000912

AC:

AN:

68004

Other (OTH)

AF:

0.0526

AC:

111

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

403

806

1209

1612

2015

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

192

288

384

480

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0210

Hom.:

637

Bravo

AF:

0.0748

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.210

AC:

927

ESP6500EA

AF:

0.00105

AC:

ExAC

AF:

0.0297

AC:

3608

Asia WGS

AF:

0.0350

AC:

123

AN:

3478

EpiCase

AF:

0.00131

EpiControl

AF:

0.000771

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Oct 01, 2013

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Atrioventricular septal defect, susceptibility to, 2

Benign:1

Feb 02, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.095

BayesDel_addAF

Benign

-0.75

BayesDel_noAF

Benign

-0.71

CADD

Benign

2.7

(source)

DANN

Benign

0.53

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.0019

LIST_S2

Benign

0.18

MetaRNN

Benign

0.0027

MetaSVM

Benign

-1.0

PhyloP100

-0.30

PrimateAI

Benign

0.29

PROVEAN

Benign

1.2

REVEL

Benign

0.051

Sift

Benign

1.0

Sift4G

Benign

0.75

Polyphen

0.0

Vest4

0.027

MPC

0.18

ClinPred

0.000023

GERP RS

1.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

gMVP

0.49

Mutation Taster

=100/0

polymorphism (auto)

(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

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over