3-9934176-T-C

Variant names:

• chr3-9934176-T-C
• rs9853613
• ENST00000383811.8:c.-263T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001077415.3(CRELD1):​c.-19-244T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0115 in 543,184 control chromosomes in the GnomAD database, including 333 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.031 (259 hom., cov: 31)
  • Exomes 𝑓: 0.0039 (74 hom.)
• Consequence: CRELD1 NM_001077415.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0260
• Publications: 1 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
• atrioventricular septal defect, susceptibility to, 2

  Inheritance: AD Classification: MODERATE, LIMITED Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae), G2P
• Jeffries-Lakhani neurodevelopmental syndrome

  Inheritance: AR Classification: MODERATE Submitted by: G2P
• 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 (BayesDel_noAF=-0.79).
• BP6: Variant 3-9934176-T-C is Benign according to our data. Variant chr3-9934176-T-C is described in ClinVar as [Benign]. Clinvar id is 1279512.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.104 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CRELD1	NM_001077415.3	c.-19-244T>C		intron_variant	Intron 1 of 10	ENST00000452070.6	NP_001070883.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CRELD1	ENST00000452070.6	c.-19-244T>C		intron_variant	Intron 1 of 10	2	NM_001077415.3	ENSP00000393643.2
ENSG00000288550	ENST00000683484.1	n.1400-659T>C		intron_variant	Intron 16 of 23			ENSP00000507040.1

Frequencies

GnomAD3 genomes AF: 0.0308 AC: 4689 AN: 152098 Hom.: 255 Cov.: 31

Gnomad AFR AF: 0.107

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0124

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000397

Gnomad OTH AF: 0.0258

GnomAD4 exome AF: 0.00391 AC: 1529 AN: 390968 Hom.: 74 Cov.: 0 AF XY: 0.00337 AC XY: 693 AN XY: 205338

African (AFR) AF: 0.101 AC: 1138 AN: 11252

American (AMR) AF: 0.00717 AC: 119 AN: 16608

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 12210

East Asian (EAS) AF: 0.00 AC: 0 AN: 25860

South Asian (SAS) AF: 0.0000698 AC: 3 AN: 42960

European-Finnish (FIN) AF: 0.0000405 AC: 1 AN: 24686

Middle Eastern (MID) AF: 0.00177 AC: 3 AN: 1698

European-Non Finnish (NFE) AF: 0.000283 AC: 66 AN: 233008

Other (OTH) AF: 0.00877 AC: 199 AN: 22686

GnomAD4 genome AF: 0.0309 AC: 4704 AN: 152216 Hom.: 259 Cov.: 31 AF XY: 0.0299 AC XY: 2228 AN XY: 74426

African (AFR) AF: 0.107 AC: 4430 AN: 41502

American (AMR) AF: 0.0124 AC: 190 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.000415 AC: 2 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10602

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000397 AC: 27 AN: 68024

Other (OTH) AF: 0.0256 AC: 54 AN: 2112

Alfa AF: 0.0176 Hom.: 29

Bravo AF: 0.0356

Asia WGS AF: 0.00808 AC: 28 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

May 17, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	5.2
DANN	Benign	0.70
PhyloP100		-0.026
PromoterAI		0.051	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs9853613; hg19: chr3-9975860;