rs121912627

Variant names:

• chr3-9944556-G-A
• rs121912627
• NM_001077415.3:c.1240G>A

Your query was ambiguous. Multiple possible variants found:

• chr3-9944556-G-A
• chr3-9944556-G-C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001077415.3(CRELD1):​c.1240G>A​(p.Glu414Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as risk factor (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E414D) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CRELD1 NM_001077415.3 missense
• Clinical Significance: risk factor no assertion criteria provided O:1
• Conservation: PhyloP100: 9.53
• Publications: 4 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]

ENSG00000288550 (HGNC:):

PRRT3 (HGNC:26591): (proline rich transmembrane protein 3) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.24425867).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001077415.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CRELD1	NM_001077415.3	MANE Select	c.1240G>A	p.Glu414Lys	missense	Exon 11 of 11	NP_001070883.2
	CRELD1	NM_001374316.1		c.1240G>A	p.Glu414Lys	missense	Exon 11 of 11	NP_001361245.1
	CRELD1	NM_015513.6		c.1240G>A	p.Glu414Lys	missense	Exon 10 of 10	NP_056328.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CRELD1	ENST00000452070.6	TSL:2 MANE Select	c.1240G>A	p.Glu414Lys	missense	Exon 11 of 11	ENSP00000393643.2
	CRELD1	ENST00000383811.8	TSL:1	c.1240G>A	p.Glu414Lys	missense	Exon 10 of 10	ENSP00000373322.3
	ENSG00000288550	ENST00000683484.1		n.*888G>A		non_coding_transcript_exon	Exon 24 of 24	ENSP00000507040.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: risk factor

Submissions summary: Other:1

Revision: no assertion criteria provided

Submissions by phenotype

Atrioventricular septal defect, susceptibility to, 2 Other:1

Oct 05, 2012

OMIM

Significance: risk factor

Review Status: no assertion criteria provided

Collection Method: literature only

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.56
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.070
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0024	T
Eigen	Uncertain	0.24
Eigen_PC	Uncertain	0.41
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.038	D
MetaRNN	Benign	0.24	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		9.5
PROVEAN	Benign	-0.64	N
REVEL	Benign	0.20
Sift	Uncertain	0.021	D
Sift4G	Uncertain	0.010	D
Polyphen		0.65	P
Vest4		0.32
MutPred		0.60		Gain of MoRF binding (P = 4e-04)
MVP		0.56
ClinPred		0.61	D
GERP RS		5.3
Varity_R		0.15
Mutation Taster		=3/97	disease causing

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: rs121912627; hg19: chr3-9986240;