rs2302787

Variant names:

• chr3-9938029-C-G
• rs2302787
• NM_001077415.3:c.383C>G
• CRELD1 p.Pro128Arg

Your query was ambiguous. Multiple possible variants found:

• chr3-9938029-C-G
• chr3-9938029-C-A
• chr3-9938029-C-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001077415.3(CRELD1):​c.383C>G​(p.Pro128Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00157 in 1,613,702 control chromosomes in the GnomAD database, including 44 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0020 (3 hom., cov: 31)
  • Exomes 𝑓: 0.0015 (41 hom.)
• Consequence: CRELD1 NM_001077415.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 7.51
• Publications: 10 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
• Jeffries-Lakhani neurodevelopmental syndrome

  Inheritance: AR Classification: MODERATE Submitted by: G2P
• atrioventricular septal defect, susceptibility to, 2

  Inheritance: AD Classification: LIMITED Submitted by: G2P, Labcorp Genetics (formerly Invitae)
• congenital heart disease

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen

ENSG00000288550 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.009946257).
• BP6: Variant 3-9938029-C-G is Benign according to our data. Variant chr3-9938029-C-G is described in ClinVar as Benign. ClinVar VariationId is 238217.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.00198 (301/152276) while in subpopulation EAS AF = 0.0502 (260/5180). AF 95% confidence interval is 0.0452. There are 3 homozygotes in GnomAd4. There are 182 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 3 AD,AR gene

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CRELD1	NM_001077415.3	MANE Select	c.383C>G	p.Pro128Arg	missense	Exon 5 of 11	NP_001070883.2	Q96HD1-1
	CRELD1	NM_001374317.1		c.383C>G	p.Pro128Arg	missense	Exon 5 of 12	NP_001361246.1	A0A804HJJ0
	CRELD1	NM_001374318.1		c.383C>G	p.Pro128Arg	missense	Exon 4 of 11	NP_001361247.1	A0A804HJJ0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CRELD1	ENST00000452070.6	TSL:2 MANE Select	c.383C>G	p.Pro128Arg	missense	Exon 5 of 11	ENSP00000393643.2	Q96HD1-1
	CRELD1	ENST00000326434.9	TSL:1	c.383C>G	p.Pro128Arg	missense	Exon 5 of 12	ENSP00000321856.5	Q96HD1-2
	CRELD1	ENST00000383811.8	TSL:1	c.383C>G	p.Pro128Arg	missense	Exon 4 of 10	ENSP00000373322.3	Q96HD1-1

Frequencies

GnomAD3 genomes AF: 0.00198 AC: 302 AN: 152158 Hom.: 3 Cov.: 31

Gnomad AFR AF: 0.000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000393

Gnomad ASJ AF: 0.000865

Gnomad EAS AF: 0.0503

Gnomad SAS AF: 0.00290

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.00144

GnomAD2 exomes AF: 0.00448 AC: 1123 AN: 250454 AF XY: 0.00428

Gnomad AFR exome AF: 0.000247

Gnomad AMR exome AF: 0.000145

Gnomad ASJ exome AF: 0.000597

Gnomad EAS exome AF: 0.0567

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000707

Gnomad OTH exome AF: 0.00196

GnomAD4 exome AF: 0.00153 AC: 2236 AN: 1461426 Hom.: 41 Cov.: 31 AF XY: 0.00154 AC XY: 1118 AN XY: 727004

African (AFR) AF: 0.000179 AC: 6 AN: 33468

American (AMR) AF: 0.000112 AC: 5 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.000459 AC: 12 AN: 26134

East Asian (EAS) AF: 0.0452 AC: 1793 AN: 39698

South Asian (SAS) AF: 0.00186 AC: 160 AN: 86222

European-Finnish (FIN) AF: 0.0000188 AC: 1 AN: 53314

Middle Eastern (MID) AF: 0.000178 AC: 1 AN: 5610

European-Non Finnish (NFE) AF: 0.0000549 AC: 61 AN: 1111904

Other (OTH) AF: 0.00326 AC: 197 AN: 60358

GnomAD4 genome AF: 0.00198 AC: 301 AN: 152276 Hom.: 3 Cov.: 31 AF XY: 0.00244 AC XY: 182 AN XY: 74468

African (AFR) AF: 0.000241 AC: 10 AN: 41550

American (AMR) AF: 0.000392 AC: 6 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.000865 AC: 3 AN: 3470

East Asian (EAS) AF: 0.0502 AC: 260 AN: 5180

South Asian (SAS) AF: 0.00290 AC: 14 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000735 AC: 5 AN: 68020

Other (OTH) AF: 0.00142 AC: 3 AN: 2112

Alfa AF: 0.000218 Hom.: 0

Bravo AF: 0.00209

Asia WGS AF: 0.0270 AC: 95 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.00

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not specified (2)
-	-	1	Atrioventricular septal defect, susceptibility to, 2 (1)
-	-	1	CRELD1-related disorder (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.080	T
BayesDel_noAF	Pathogenic	0.15
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Benign	0.21	T
Eigen	Pathogenic	0.75
Eigen_PC	Pathogenic	0.70
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.91	D
MetaRNN	Benign	0.0099	T
MetaSVM	Benign	-0.84	T
MutationAssessor	Uncertain	2.8	M
PhyloP100		7.5
PrimateAI	Uncertain	0.58	T
PROVEAN	Pathogenic	-8.6	D
REVEL	Uncertain	0.56
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.013	D
Varity_R		0.64
gMVP		0.88
Mutation Taster		=80/20	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs2302787;

hg19: chr3-9979713;

COSMIC: COSV107353408;

COSMIC: COSV107353408;