3-9934451-C-G

Variant names:

• chr3-9934451-C-G
• rs763567262
• NM_001077415.3:c.13C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001077415.3(CRELD1):​c.13C>G​(p.Pro5Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P5T) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: CRELD1 NM_001077415.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.914
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AR Classification: STRONG Submitted by: Ambry Genetics
• atrioventricular septal defect, susceptibility to, 2

  Inheritance: AD Classification: MODERATE, LIMITED Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae), G2P
• Jeffries-Lakhani neurodevelopmental syndrome

  Inheritance: AR Classification: MODERATE Submitted by: G2P
• congenital heart disease

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen

ENSG00000288550 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.059673876).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CRELD1	NM_001077415.3	c.13C>G	p.Pro5Ala	missense_variant	Exon 2 of 11	ENST00000452070.6	NP_001070883.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CRELD1	ENST00000452070.6	c.13C>G	p.Pro5Ala	missense_variant	Exon 2 of 11	2	NM_001077415.3	ENSP00000393643.2
ENSG00000288550	ENST00000683484.1	n.1400-384C>G		intron_variant	Intron 16 of 23			ENSP00000507040.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.062
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	1.2
DANN	Benign	0.36
DEOGEN2	Benign	0.0043	T;T;T;.
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.079	N
LIST_S2	Benign	0.62	.;.;T;T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.060	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N;N;N;N
PhyloP100		-0.91
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-1.1	N;N;N;N
REVEL	Benign	0.21
Sift	Benign	0.31	T;T;T;T
Sift4G	Benign	0.16	T;T;T;T
Polyphen		0.0	B;B;B;B
Vest4		0.21
MutPred		0.28		Loss of glycosylation at K6 (P = 0.0085);Loss of glycosylation at K6 (P = 0.0085);Loss of glycosylation at K6 (P = 0.0085);Loss of glycosylation at K6 (P = 0.0085);
MVP		0.37
MPC		0.16
ClinPred		0.047	T
GERP RS		-0.86
PromoterAI		0.032	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.038
gMVP		0.30
Mutation Taster		=95/5	polymorphism

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

Other links and lift over

dbSNP: rs763567262; hg19: chr3-9976135;