Variant chr3-9943412-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_001077415.3(CRELD1):c.945G>A(p.Pro315=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.014 in 1,613,998 control chromosomes in the GnomAD database, including 193 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.011 ( 13 hom., cov: 32)

Exomes 𝑓: 0.014 ( 180 hom. )

Consequence

CRELD1
NM_001077415.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -3.06

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=-0.61).

BP6

Variant 3-9943412-G-A is Benign according to our data. Variant chr3-9943412-G-A is described in ClinVar as [Benign]. Clinvar id is 137029.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-9943412-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-3.06 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0108 (1644/152168) while in subpopulation NFE AF= 0.0173 (1176/68000). AF 95% confidence interval is 0.0165. There are 13 homozygotes in gnomad4. There are 746 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1644 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CRELD1	NM_001077415.3 linkuse as main transcript	c.945G>A	p.Pro315=	synonymous_variant	10/11	ENST00000452070.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CRELD1	ENST00000452070.6 linkuse as main transcript	c.945G>A	p.Pro315=	synonymous_variant	10/11	2	NM_001077415.3	P1	Q96HD1-1

Frequencies

GnomAD3 genomes

AF:

0.0108

AC:

1644

AN:

152050

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00304

Gnomad AMI

AF:

0.0439

Gnomad AMR

AF:

0.00556

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.000582

Gnomad SAS

AF:

0.00290

Gnomad FIN

AF:

0.0161

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0173

Gnomad OTH

AF:

0.0100

GnomAD3 exomes

AF:

0.0109

AC:

2735

AN:

251330

Hom.:

AF XY:

0.0114

AC XY:

1545

AN XY:

135870

show subpopulations

Gnomad AFR exome

AF:

0.00289

Gnomad AMR exome

AF:

0.00359

Gnomad ASJ exome

AF:

0.00129

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00431

Gnomad FIN exome

AF:

0.0156

Gnomad NFE exome

AF:

0.0179

Gnomad OTH exome

AF:

0.00798

GnomAD4 exome

AF:

0.0143

AC:

20922

AN:

1461830

Hom.:

180

Cov.:

AF XY:

0.0141

AC XY:

10222

AN XY:

727220

show subpopulations

Gnomad4 AFR exome

AF:

0.00233

Gnomad4 AMR exome

AF:

0.00353

Gnomad4 ASJ exome

AF:

0.00199

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00390

Gnomad4 FIN exome

AF:

0.0170

Gnomad4 NFE exome

AF:

0.0168

Gnomad4 OTH exome

AF:

0.0116

GnomAD4 genome

AF:

0.0108

AC:

1644

AN:

152168

Hom.:

Cov.:

AF XY:

0.0100

AC XY:

746

AN XY:

74378

show subpopulations

Gnomad4 AFR

AF:

0.00303

Gnomad4 AMR

AF:

0.00556

Gnomad4 ASJ

AF:

0.00202

Gnomad4 EAS

AF:

0.000584

Gnomad4 SAS

AF:

0.00291

Gnomad4 FIN

AF:

0.0161

Gnomad4 NFE

AF:

0.0173

Gnomad4 OTH

AF:

0.00994

Alfa

AF:

0.0110

Hom.:

Bravo

AF:

0.00974

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.0149

EpiControl

AF:

0.0141

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Apr 22, 2014

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

Labcorp Genetics (formerly Invitae), Labcorp

Dec 18, 2023

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.61

CADD

Benign

0.076

DANN

Benign

0.88

RBP_binding_hub_radar

1.1

RBP_regulation_power_radar

2.8

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