3-9940964-G-C

Position:

• chr3-9940964-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001077415.3(CRELD1):​c.575G>C​(p.Cys192Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,880 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CRELD1 NM_001077415.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.53

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:):

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.855

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CRELD1	NM_001077415.3	c.575G>C	p.Cys192Ser	missense_variant	6/11	ENST00000452070.6	NP_001070883.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CRELD1	ENST00000452070.6	c.575G>C	p.Cys192Ser	missense_variant	6/11	2	NM_001077415.3	ENSP00000393643.2
ENSG00000288550	ENST00000683484.1	n.*223G>C		non_coding_transcript_exon_variant	19/24			ENSP00000507040.1
ENSG00000288550	ENST00000683484.1	n.*223G>C		3_prime_UTR_variant	19/24			ENSP00000507040.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251352 Hom.: 0 AF XY: 0.00000736 AC XY: 1 AN XY: 135880

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

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: 0.00000880

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461880 Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1 AN XY: 727240

Gnomad4 AFR exome AF: 0.00

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: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.99
BayesDel_addAF	Pathogenic	0.40	D
BayesDel_noAF	Pathogenic	0.33
CADD	Pathogenic	31
DANN	Uncertain	1.0
DEOGEN2	Benign	0.30	T;T;T;.
Eigen	Pathogenic	0.86
Eigen_PC	Pathogenic	0.83
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.73	.;.;T;T
M_CAP	Uncertain	0.10	D
MetaRNN	Pathogenic	0.86	D;D;D;D
MetaSVM	Uncertain	0.055	D
MutationAssessor	Pathogenic	3.4	M;M;M;M
PrimateAI	Uncertain	0.70	T
PROVEAN	Pathogenic	-9.6	D;D;D;D
REVEL	Uncertain	0.64
Sift	Pathogenic	0.0	D;D;D;D
Sift4G	Uncertain	0.014	D;D;D;D
Polyphen		1.0	D;D;D;D
Vest4		0.95
MutPred		0.50		Gain of loop (P = 0.1081);Gain of loop (P = 0.1081);Gain of loop (P = 0.1081);Gain of loop (P = 0.1081);
MVP		0.91
MPC		0.75
ClinPred		1.0	D
GERP RS		5.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.95
gMVP		0.98

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

Publications

LitVar

Other links and lift over

dbSNP: rs201866563; hg19: chr3-9982648;