rs3774207

Variant names:

• chr3-9943972-C-A
• rs3774207
• ENST00000326434.9:c.1119C>A

Your query was ambiguous. Multiple possible variants found:

• chr3-9943972-C-A
• chr3-9943972-C-G
• chr3-9943972-C-T

Variant summary

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

The ENST00000326434.9(CRELD1):​c.1119C>A​(p.His373Gln) 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. 16/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. H373H) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CRELD1 ENST00000326434.9 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.270
• 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]

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=0.12808251).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000326434.9. 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.1049-393C>A		intron	N/A	NP_001070883.2
	CRELD1	NM_001374317.1		c.1131C>A	p.His377Gln	missense	Exon 11 of 12	NP_001361246.1
	CRELD1	NM_001374318.1		c.1131C>A	p.His377Gln	missense	Exon 10 of 11	NP_001361247.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CRELD1	ENST00000326434.9	TSL:1	c.1119C>A	p.His373Gln	missense	Exon 11 of 12	ENSP00000321856.5
	CRELD1	ENST00000452070.6	TSL:2 MANE Select	c.1049-393C>A		intron	N/A	ENSP00000393643.2
	CRELD1	ENST00000383811.8	TSL:1	c.1049-393C>A		intron	N/A	ENSP00000373322.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 14

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.084
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	1.1
DANN	Benign	0.64
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.027	N
LIST_S2	Benign	0.33	T
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-0.97	T
PhyloP100		-0.27
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-0.040	N
REVEL	Benign	0.039
Sift	Benign	0.076	T
Sift4G	Benign	0.36	T
Polyphen		0.17	B
Vest4		0.31
MutPred		0.57		Gain of glycosylation at Y376 (P = 0.0023)
MVP		0.30
MPC		0.16
ClinPred		0.085	T
GERP RS		-1.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
gMVP		0.40
Mutation Taster		=100/0	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: rs3774207; hg19: chr3-9985656;