Variant 3-9934553-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001077415.3(CRELD1):c.115C>T(p.Pro39Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,806 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

CRELD1
NM_001077415.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.240

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0901601).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CRELD1	NM_001077415.3 linkuse as main transcript	c.115C>T	p.Pro39Ser	missense_variant	2/11	ENST00000452070.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CRELD1	ENST00000452070.6 linkuse as main transcript	c.115C>T	p.Pro39Ser	missense_variant	2/11	2	NM_001077415.3	P1	Q96HD1-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461806

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727200

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 12, 2023

The c.115C>T (p.P39S) alteration is located in exon 1 (coding exon 1) of the CRELD1 gene. This alteration results from a C to T substitution at nucleotide position 115, causing the proline (P) at amino acid position 39 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.059

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.39

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0022

T;T;T;.

Eigen

Benign

-0.47

Eigen_PC

Benign

-0.47

FATHMM_MKL

Benign

0.61

LIST_S2

Benign

0.66

.;.;T;T

M_CAP

Benign

0.026

MetaRNN

Benign

0.090

T;T;T;T

MetaSVM

Benign

-0.91

MutationAssessor

Benign

0.69

N;N;N;N

MutationTaster

Benign

0.97

N;N;N;N

PrimateAI

Benign

0.33

PROVEAN

Benign

0.47

N;N;N;N

REVEL

Benign

0.069

Sift

Benign

0.20

T;T;T;T

Sift4G

Benign

0.36

T;T;T;T

Polyphen

0.0060

B;B;B;D

Vest4

0.32

MutPred

0.32

Loss of glycosylation at P40 (P = 5e-04);Loss of glycosylation at P40 (P = 5e-04);Loss of glycosylation at P40 (P = 5e-04);Loss of glycosylation at P40 (P = 5e-04);

MVP

0.59

MPC

0.17

ClinPred

0.12

GERP RS

1.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.7

Varity_R

0.070

gMVP

0.32

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over