Variant rs28941780 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_001077415.3(CRELD1):c.320G>A(p.Arg107His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000236 in 1,612,102 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R107C) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00013 ( 0 hom. )

Consequence

CRELD1
NM_001077415.3 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications P:1U:1B:1

Conservation

PhyloP100: 1.94

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009116113).

BP6

Variant 3-9937624-G-A is Benign according to our data. Variant chr3-9937624-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 3429.We mark this variant Likely_benign, oryginal submissions are: {Benign=1, Uncertain_significance=1}.

BS2

High AC in GnomAd4 at 197 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CRELD1	NM_001077415.3 linkuse as main transcript	c.320G>A	p.Arg107His	missense_variant	4/11	ENST00000452070.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CRELD1	ENST00000452070.6 linkuse as main transcript	c.320G>A	p.Arg107His	missense_variant	4/11	2	NM_001077415.3	P1	Q96HD1-1

Frequencies

GnomAD3 genomes

AF:

0.00129

AC:

197

AN:

152140

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00451

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000524

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:

0.000956

GnomAD3 exomes

AF:

0.000346

AC:

AN:

245458

Hom.:

AF XY:

0.000272

AC XY:

AN XY:

132526

show subpopulations

Gnomad AFR exome

AF:

0.00488

Gnomad AMR exome

AF:

0.000146

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000271

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000126

AC:

184

AN:

1459844

Hom.:

Cov.:

AF XY:

0.000116

AC XY:

AN XY:

725928

show subpopulations

Gnomad4 AFR exome

AF:

0.00397

Gnomad4 AMR exome

AF:

0.000270

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000180

Gnomad4 OTH exome

AF:

0.000298

GnomAD4 genome

AF:

0.00129

AC:

197

AN:

152258

Hom.:

Cov.:

AF XY:

0.00132

AC XY:

AN XY:

74438

show subpopulations

Gnomad4 AFR

AF:

0.00450

Gnomad4 AMR

AF:

0.000523

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000946

Alfa

AF:

0.000342

Hom.:

Bravo

AF:

0.00142

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.00318

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000470

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Pathogenic:1Uncertain:1Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

Atrioventricular septal defect, partial, with heterotaxy syndrome

Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Mar 31, 2014

- -

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Eurofins Ntd Llc (ga)

Jan 13, 2016

- -

Atrioventricular septal defect, susceptibility to, 2

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Aug 16, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.067

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.18

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.0023

T;T;T;.

Eigen

Uncertain

0.37

Eigen_PC

Uncertain

0.42

FATHMM_MKL

Uncertain

0.83

LIST_S2

Uncertain

0.90

.;.;D;D

M_CAP

Benign

0.015

MetaRNN

Benign

0.0091

T;T;T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

0.34

N;N;N;N

MutationTaster

Benign

0.85

A;A;A;A

PrimateAI

Uncertain

0.51

PROVEAN

Benign

-0.56

N;N;N;N

REVEL

Benign

0.21

Sift

Benign

0.23

T;T;T;T

Sift4G

Benign

0.25

T;T;T;T

Polyphen

1.0

D;D;D;D

Vest4

0.74

MVP

0.40

MPC

0.72

ClinPred

0.025

GERP RS

5.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.062

gMVP

0.57

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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