rs920334740

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The ENST00000326434.9(CRELD1):c.1123A>G(p.Thr375Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000926 in 1,079,760 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000086 ( 0 hom. )

Consequence

CRELD1
ENST00000326434.9 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.409

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 -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.05924523).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CRELD1	NM_001077415.3 link	c.1049-389A>G		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.1049-389A>G		intron_variant	Intron 10 of 10	2	NM_001077415.3	ENSP00000393643.2		Q96HD1-1
ENSG00000288550	ENST00000683484.1 link	n.*697-389A>G		intron_variant	Intron 23 of 23			ENSP00000507040.1		A0A804HIF2

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152136

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000241

AC:

AN:

249054

AF XY:

0.0000223

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000116

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000898

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.00000862

AC:

AN:

927624

Hom.:

Cov.:

AF XY:

0.00000620

AC XY:

AN XY:

483690

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

23178

American (AMR)

AF:

0.000136

AC:

AN:

44074

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22804

East Asian (EAS)

AF:

0.00

AC:

AN:

37302

South Asian (SAS)

AF:

0.00

AC:

AN:

75514

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53236

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4714

European-Non Finnish (NFE)

AF:

0.00000321

AC:

AN:

623788

Other (OTH)

AF:

0.00

AC:

AN:

43014

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

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

AF:

0.0000131

AC:

AN:

152136

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74332

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41418

American (AMR)

AF:

0.000131

AC:

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68022

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.0000329

Hom.:

Bravo

AF:

0.0000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Atrioventricular septal defect, susceptibility to, 2

Uncertain:1

May 13, 2017

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Algorithms developed to predict the effect of missense changes on protein structure and function (PolyPhen-2, Align-GVGD) suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies. In summary, this variant is a novel missense change that is not predicted to affect protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a CRELD1-related disease. This sequence change replaces threonine with alanine at codon 375 of the CRELD1 protein (p.Thr375Ala). The threonine residue is weakly conserved and there is a small physicochemical difference between threonine and alanine. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.061

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.67

CADD

Benign

1.2

(source)

DANN

Benign

0.79

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.037

LIST_S2

Benign

0.26

M_CAP

Benign

0.013

MetaRNN

Benign

0.059

MetaSVM

Benign

-1.0

PhyloP100

-0.41

PrimateAI

Benign

0.24

PROVEAN

Benign

0.15

REVEL

Benign

0.075

Sift

Benign

0.13

Sift4G

Benign

0.28

Polyphen

0.0

Vest4

0.015

MutPred

0.51

Gain of glycosylation at Y376 (P = 0.0023);

MVP

0.26

MPC

0.16

ClinPred

0.028

GERP RS

-0.066

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

gMVP

0.34

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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