3-9943171-C-T

Variant summary

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

The NM_001077415.3(CRELD1):c.912C>T(p.Leu304=) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00366 in 1,612,092 control chromosomes in the GnomAD database, including 183 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.019 ( 89 hom., cov: 32)

Exomes 𝑓: 0.0021 ( 94 hom. )

Consequence

CRELD1
NM_001077415.3 splice_region, synonymous

Scores

Splicing: ADA: 0.0009384

Clinical Significance

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

Conservation

PhyloP100: -0.883

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=-0.51).

BP6

Variant 3-9943171-C-T is Benign according to our data. Variant chr3-9943171-C-T is described in ClinVar as [Benign]. Clinvar id is 137034.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-9943171-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.883 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0637 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.912C>T	p.Leu304=	splice_region_variant, synonymous_variant	9/11	ENST00000452070.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CRELD1	ENST00000452070.6 linkuse as main transcript	c.912C>T	p.Leu304=	splice_region_variant, synonymous_variant	9/11	2	NM_001077415.3	P1	Q96HD1-1

Frequencies

GnomAD3 genomes

AF:

0.0187

AC:

2851

AN:

152104

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0658

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00569

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00124

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000250

Gnomad OTH

AF:

0.00813

GnomAD3 exomes

AF:

0.00481

AC:

1204

AN:

250550

Hom.:

AF XY:

0.00346

AC XY:

469

AN XY:

135476

show subpopulations

Gnomad AFR exome

AF:

0.0656

Gnomad AMR exome

AF:

0.00281

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000294

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000158

Gnomad OTH exome

AF:

0.00261

GnomAD4 exome

AF:

0.00208

AC:

3043

AN:

1459870

Hom.:

Cov.:

AF XY:

0.00181

AC XY:

1312

AN XY:

726272

show subpopulations

Gnomad4 AFR exome

AF:

0.0688

Gnomad4 AMR exome

AF:

0.00362

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000383

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000250

Gnomad4 OTH exome

AF:

0.00417

GnomAD4 genome

AF:

0.0188

AC:

2857

AN:

152222

Hom.:

Cov.:

AF XY:

0.0183

AC XY:

1364

AN XY:

74420

show subpopulations

Gnomad4 AFR

AF:

0.0658

Gnomad4 AMR

AF:

0.00562

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00124

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000250

Gnomad4 OTH

AF:

0.00805

Alfa

AF:

0.00311

Hom.:

Bravo

AF:

0.0205

Asia WGS

AF:

0.00260

AC:

AN:

3478

EpiCase

AF:

0.000382

EpiControl

AF:

0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jan 16, 2013

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

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.51

Cadd

Benign

Dann

Benign

0.78

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.7

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00094

dbscSNV1_RF

Benign

0.21

SpliceAI score (max)

0.090

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