3-9940761-A-G

Position:

• chr3-9940761-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001077415.3(CRELD1):​c.461-89A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.147 in 840,194 control chromosomes in the GnomAD database, including 5,702 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.14 (232 hom., cov: 15)
  • Exomes 𝑓: 0.15 (5470 hom.)
• Consequence: CRELD1 NM_001077415.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.19

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BP6: Variant 3-9940761-A-G is Benign according to our data. Variant chr3-9940761-A-G is described in ClinVar as [Benign]. Clinvar id is 1263162.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.161 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CRELD1	NM_001077415.3	c.461-89A>G		intron_variant		ENST00000452070.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CRELD1	ENST00000452070.6	c.461-89A>G		intron_variant		2	NM_001077415.3	P1

Frequencies

GnomAD3 genomes AF: 0.143 AC: 14859 AN: 103974 Hom.: 232 Cov.: 15

Gnomad AFR AF: 0.166

Gnomad AMI AF: 0.223

Gnomad AMR AF: 0.132

Gnomad ASJ AF: 0.139

Gnomad EAS AF: 0.115

Gnomad SAS AF: 0.155

Gnomad FIN AF: 0.0842

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.148

Gnomad OTH AF: 0.135

GnomAD4 exome AF: 0.148 AC: 108653 AN: 736156 Hom.: 5470 AF XY: 0.149 AC XY: 57009 AN XY: 383610

Gnomad4 AFR exome AF: 0.119

Gnomad4 AMR exome AF: 0.192

Gnomad4 ASJ exome AF: 0.130

Gnomad4 EAS exome AF: 0.157

Gnomad4 SAS exome AF: 0.162

Gnomad4 FIN exome AF: 0.100

Gnomad4 NFE exome AF: 0.148

Gnomad4 OTH exome AF: 0.137

GnomAD4 genome AF: 0.143 AC: 14861 AN: 104038 Hom.: 232 Cov.: 15 AF XY: 0.135 AC XY: 6817 AN XY: 50318

Gnomad4 AFR AF: 0.166

Gnomad4 AMR AF: 0.132

Gnomad4 ASJ AF: 0.139

Gnomad4 EAS AF: 0.114

Gnomad4 SAS AF: 0.156

Gnomad4 FIN AF: 0.0842

Gnomad4 NFE AF: 0.148

Gnomad4 OTH AF: 0.132

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 11, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.91
DANN	Benign	0.13
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs55862344; hg19: chr3-9982445;