Variant chr3-9943972-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The ENST00000326434.9(CRELD1):c.1119C>T(p.His373=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.27 in 1,106,654 control chromosomes in the GnomAD database, including 48,973 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.37 ( 13892 hom., cov: 32)

Exomes 𝑓: 0.25 ( 35081 hom. )

Consequence

CRELD1
ENST00000326434.9 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.270

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:

(HGNC:):

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 made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 3-9943972-C-T is Benign according to our data. Variant chr3-9943972-C-T is described in ClinVar as [Benign]. Clinvar id is 137030.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-9943972-C-T is described in Lovd as [Benign]. Variant chr3-9943972-C-T is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=-0.27 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.708 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CRELD1	NM_001077415.3 linkuse as main transcript	c.1049-393C>T		intron_variant		ENST00000452070.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CRELD1	ENST00000452070.6 linkuse as main transcript	c.1049-393C>T		intron_variant		2	NM_001077415.3	P1	Q96HD1-1

Frequencies

GnomAD3 genomes

AF:

0.367

AC:

55816

AN:

151994

Hom.:

13874

Cov.:

show subpopulations

Gnomad AFR

AF:

0.715

Gnomad AMI

AF:

0.326

Gnomad AMR

AF:

0.277

Gnomad ASJ

AF:

0.291

Gnomad EAS

AF:

0.185

Gnomad SAS

AF:

0.265

Gnomad FIN

AF:

0.151

Gnomad MID

AF:

0.241

Gnomad NFE

AF:

0.237

Gnomad OTH

AF:

0.323

GnomAD3 exomes

AF:

0.272

AC:

67640

AN:

249032

Hom.:

11498

AF XY:

0.262

AC XY:

35309

AN XY:

134808

show subpopulations

Gnomad AFR exome

AF:

0.730

Gnomad AMR exome

AF:

0.308

Gnomad ASJ exome

AF:

0.294

Gnomad EAS exome

AF:

0.183

Gnomad SAS exome

AF:

0.253

Gnomad FIN exome

AF:

0.159

Gnomad NFE exome

AF:

0.234

Gnomad OTH exome

AF:

0.252

GnomAD4 exome

AF:

0.254

AC:

242391

AN:

954542

Hom.:

35081

Cov.:

AF XY:

0.252

AC XY:

125093

AN XY:

496204

show subpopulations

Gnomad4 AFR exome

AF:

0.727

Gnomad4 AMR exome

AF:

0.308

Gnomad4 ASJ exome

AF:

0.291

Gnomad4 EAS exome

AF:

0.225

Gnomad4 SAS exome

AF:

0.260

Gnomad4 FIN exome

AF:

0.164

Gnomad4 NFE exome

AF:

0.239

Gnomad4 OTH exome

AF:

0.271

GnomAD4 genome

AF:

0.367

AC:

55884

AN:

152112

Hom.:

13892

Cov.:

AF XY:

0.357

AC XY:

26525

AN XY:

74368

show subpopulations

Gnomad4 AFR

AF:

0.714

Gnomad4 AMR

AF:

0.276

Gnomad4 ASJ

AF:

0.291

Gnomad4 EAS

AF:

0.186

Gnomad4 SAS

AF:

0.266

Gnomad4 FIN

AF:

0.151

Gnomad4 NFE

AF:

0.237

Gnomad4 OTH

AF:

0.321

Alfa

AF:

0.270

Hom.:

9848

Bravo

AF:

0.395

Asia WGS

AF:

0.232

AC:

809

AN:

3478

EpiCase

AF:

0.245

EpiControl

AF:

0.238

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 31, 2012	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. -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -

not provided

Benign:2

Likely benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Atrioventricular septal defect, susceptibility to, 2

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

1.1

DANN

Benign

0.46

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over