3-9934475-A-G

Variant names:

Variant summary

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

The NM_001077415.3(CRELD1):c.37A>G(p.Met13Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.99 in 1,613,982 control chromosomes in the GnomAD database, including 790,642 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.99 ( 74939 hom., cov: 30)

Exomes 𝑓: 0.99 ( 715703 hom. )

Consequence

CRELD1
NM_001077415.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.403

Publications

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

BP4

Computational evidence support a benign effect (MetaRNN=9.5156565E-7).

BP6

Variant 3-9934475-A-G is Benign according to our data. Variant chr3-9934475-A-G is described in ClinVar as [Benign]. Clinvar id is 1164100.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.99 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CRELD1	NM_001077415.3 link	c.37A>G	p.Met13Val	missense_variant	Exon 2 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.37A>G	p.Met13Val	missense_variant	Exon 2 of 11	2	NM_001077415.3	ENSP00000393643.2		Q96HD1-1
ENSG00000288550	ENST00000683484.1 link	n.1400-360A>G		intron_variant	Intron 16 of 23			ENSP00000507040.1		A0A804HIF2

Frequencies

GnomAD3 genomes

AF:

0.992

AC:

150936

AN:

152132

Hom.:

74878

Cov.:

show subpopulations

Gnomad AFR

AF:

0.998

Gnomad AMI

AF:

1.00

Gnomad AMR

AF:

0.991

Gnomad ASJ

AF:

0.988

Gnomad EAS

AF:

1.00

Gnomad SAS

AF:

0.990

Gnomad FIN

AF:

0.998

Gnomad MID

AF:

0.997

Gnomad NFE

AF:

0.988

Gnomad OTH

AF:

0.990

GnomAD2 exomes

AF:

0.991

AC:

249146

AN:

251350

AF XY:

0.991

show subpopulations

Gnomad AFR exome

AF:

0.998

Gnomad AMR exome

AF:

0.993

Gnomad ASJ exome

AF:

0.990

Gnomad EAS exome

AF:

1.00

Gnomad FIN exome

AF:

0.998

Gnomad NFE exome

AF:

0.988

Gnomad OTH exome

AF:

0.992

GnomAD4 exome

AF:

0.990

AC:

1446473

AN:

1461732

Hom.:

715703

Cov.:

AF XY:

0.990

AC XY:

719552

AN XY:

727168

show subpopulations

African (AFR)

AF:

0.998

AC:

33417

AN:

33476

American (AMR)

AF:

0.993

AC:

44399

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.989

AC:

25845

AN:

26134

East Asian (EAS)

AF:

1.00

AC:

39698

AN:

39700

South Asian (SAS)

AF:

0.989

AC:

85303

AN:

86254

European-Finnish (FIN)

AF:

0.997

AC:

53186

AN:

53344

Middle Eastern (MID)

AF:

0.990

AC:

5710

AN:

5768

European-Non Finnish (NFE)

AF:

0.988

AC:

1099081

AN:

1111944

Other (OTH)

AF:

0.991

AC:

59834

AN:

60388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

838

1675

2513

3350

4188

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.992

AC:

151056

AN:

152250

Hom.:

74939

Cov.:

AF XY:

0.992

AC XY:

73843

AN XY:

74428

show subpopulations

African (AFR)

AF:

0.998

AC:

41466

AN:

41556

American (AMR)

AF:

0.991

AC:

15139

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.988

AC:

3432

AN:

3472

East Asian (EAS)

AF:

1.00

AC:

5165

AN:

5166

South Asian (SAS)

AF:

0.990

AC:

4783

AN:

4830

European-Finnish (FIN)

AF:

0.998

AC:

10581

AN:

10602

Middle Eastern (MID)

AF:

1.00

AC:

294

AN:

294

European-Non Finnish (NFE)

AF:

0.988

AC:

67194

AN:

68026

Other (OTH)

AF:

0.991

AC:

2090

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

135

202

270

337

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.990

Hom.:

243417

Bravo

AF:

0.992

TwinsUK

AF:

0.989

AC:

3669

ALSPAC

AF:

0.991

AC:

3818

ESP6500AA

AF:

0.998

AC:

4399

ESP6500EA

AF:

0.988

AC:

8496

ExAC

AF:

0.992

AC:

120388

Asia WGS

AF:

0.997

AC:

3466

AN:

3478

EpiCase

AF:

0.987

EpiControl

AF:

0.988

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Atrioventricular septal defect, susceptibility to, 2

Benign:1

Feb 04, 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

0.056

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.60

CADD

Benign

1.6

(source)

DANN

Benign

0.68

DEOGEN2

Benign

0.00068

T;T;T;.

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.026

LIST_S2

Benign

0.12

.;.;T;T

MetaRNN

Benign

9.5e-7

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.34

N;N;N;N

PhyloP100

-0.40

PrimateAI

Benign

0.38

PROVEAN

Benign

-0.11

N;N;N;N

REVEL

Benign

0.064

Sift

Benign

0.55

T;T;T;T

Sift4G

Benign

0.86

T;T;T;T

Polyphen

0.0

B;B;B;B

Vest4

0.061

MPC

0.16

ClinPred

0.0013

GERP RS

0.33

PromoterAI

0.014

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.032

gMVP

0.21

Mutation Taster

=100/0

polymorphism (auto)

(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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3-9934475-A-G

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