rs200024536

chr3-9941005-G-Achr3-9941005-G-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001077415.3(CRELD1):c.616G>A(p.Ala206Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00038 in 1,614,190 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00028 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00039 (6 hom.)
• Consequence: CRELD1 NM_001077415.3 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.294

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]

(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

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.007459134).
• BP6: Variant 3-9941005-G-A is Benign according to our data. Variant chr3-9941005-G-A is described in ClinVar as [Benign]. Clinvar id is 414254.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd at 43 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CRELD1	NM_001077415.3	c.616G>A	p.Ala206Thr	missense_variant	6/11	ENST00000452070.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CRELD1	ENST00000452070.6	c.616G>A	p.Ala206Thr	missense_variant	6/11	2	NM_001077415.3	P1

Frequencies

GnomAD3 genomes AF: 0.000283 AC: 43 AN: 152188 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00268

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.00205 AC: 516 AN: 251366 Hom.: 5 AF XY: 0.00169 AC XY: 229 AN XY: 135868

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0146

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: 0.00163

GnomAD4 exome AF: 0.000390 AC: 570 AN: 1461884 Hom.: 6 Cov.: 33 AF XY: 0.000322 AC XY: 234 AN XY: 727244

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0124

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: 0.00000540

Gnomad4 OTH exome AF: 0.000132

GnomAD4 genome AF: 0.000282 AC: 43 AN: 152306 Hom.: 0 Cov.: 31 AF XY: 0.000201 AC XY: 15 AN XY: 74468

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00268

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000294

Gnomad4 OTH AF: 0.00

Alfa AF: 0.0000665 Hom.: 0

Bravo AF: 0.000797

ExAC AF: 0.00163 AC: 198

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Atrioventricular septal defect, susceptibility to, 2 Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Nov 27, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.068
BayesDel_addAF	Benign	-0.61	T
BayesDel_noAF	Benign	-0.63
Cadd	Benign	13
Dann	Benign	0.97
DEOGEN2	Benign	0.0012	T;T;T;.
Eigen	Benign	-0.71
Eigen_PC	Benign	-0.58
FATHMM_MKL	Benign	0.33	N
MetaRNN	Benign	0.0075	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.090	N;N;N;N
MutationTaster	Benign	1.0	N;N;N;N
PrimateAI	Benign	0.36	T
PROVEAN	Benign	0.25	N;N;N;N
REVEL	Benign	0.022
Sift	Benign	0.24	T;T;T;T
Sift4G	Benign	0.55	T;T;T;T
Polyphen		0.0	B;B;B;B
Vest4		0.11
MVP		0.52
MPC		0.16
ClinPred		0.018	T
GERP RS		-1.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.039
gMVP		0.38

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs200024536; hg19: chr3-9982689; COSMIC: COSV55977146; COSMIC: COSV55977146;