3-9935180-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001077415.3(CRELD1):c.257+263C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.216 in 421,818 control chromosomes in the GnomAD database, including 10,580 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.24 (4698 hom., cov: 32)
  • Exomes 𝑓: 0.21 (5882 hom.)
• Consequence: CRELD1 NM_001077415.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.12

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:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 3-9935180-C-T is Benign according to our data. Variant chr3-9935180-C-T is described in ClinVar as [Benign]. Clinvar id is 1223326.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr3-9935180-C-T is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.351 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CRELD1	NM_001077415.3	c.257+263C>T		intron_variant		ENST00000452070.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CRELD1	ENST00000452070.6	c.257+263C>T		intron_variant		2	NM_001077415.3	P1

Frequencies

GnomAD3 genomes AF: 0.235 AC: 35735 AN: 151840 Hom.: 4692 Cov.: 32

Gnomad AFR AF: 0.356

Gnomad AMI AF: 0.333

Gnomad AMR AF: 0.205

Gnomad ASJ AF: 0.165

Gnomad EAS AF: 0.140

Gnomad SAS AF: 0.200

Gnomad FIN AF: 0.144

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.196

Gnomad OTH AF: 0.213

GnomAD4 exome AF: 0.206 AC: 55502 AN: 269858 Hom.: 5882 AF XY: 0.206 AC XY: 29507 AN XY: 143068

Gnomad4 AFR exome AF: 0.365

Gnomad4 AMR exome AF: 0.235

Gnomad4 ASJ exome AF: 0.179

Gnomad4 EAS exome AF: 0.169

Gnomad4 SAS exome AF: 0.213

Gnomad4 FIN exome AF: 0.157

Gnomad4 NFE exome AF: 0.202

Gnomad4 OTH exome AF: 0.207

GnomAD4 genome AF: 0.235 AC: 35763 AN: 151960 Hom.: 4698 Cov.: 32 AF XY: 0.229 AC XY: 17039 AN XY: 74260

Gnomad4 AFR AF: 0.356

Gnomad4 AMR AF: 0.205

Gnomad4 ASJ AF: 0.165

Gnomad4 EAS AF: 0.140

Gnomad4 SAS AF: 0.202

Gnomad4 FIN AF: 0.144

Gnomad4 NFE AF: 0.196

Gnomad4 OTH AF: 0.210

Alfa AF: 0.216 Hom.: 785

Bravo AF: 0.248

Asia WGS AF: 0.169 AC: 588 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 19, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	1.1
Dann	Benign	0.66

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: rs3901800; hg19: chr3-9976864;