3-9933888-C-T

Variant names:

• chr3-9933888-C-T
• rs59211226
• NM_001077415.3:c.-52C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001077415.3(CRELD1):​c.-52C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0123 in 459,486 control chromosomes in the GnomAD database, including 300 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.031 (255 hom., cov: 31)
  • Exomes 𝑓: 0.0032 (45 hom.)
• Consequence: CRELD1 NM_001077415.3 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.488
• Publications: 0 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BP6: Variant 3-9933888-C-T is Benign according to our data. Variant chr3-9933888-C-T is described in ClinVar as [Benign]. Clinvar id is 1259816.Status of the report is criteria_provided_single_submitter, 1 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.-52C>T		5_prime_UTR_variant	Exon 1 of 11	ENST00000452070.6	NP_001070883.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CRELD1	ENST00000452070.6	c.-52C>T		5_prime_UTR_variant	Exon 1 of 11	2	NM_001077415.3	ENSP00000393643.2
ENSG00000288550	ENST00000683484.1	n.1400-947C>T		intron_variant	Intron 16 of 23			ENSP00000507040.1

Frequencies

GnomAD3 genomes AF: 0.0306 AC: 4650 AN: 152046 Hom.: 254 Cov.: 31

Gnomad AFR AF: 0.107

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0100

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.000221

Gnomad OTH AF: 0.0244

GnomAD4 exome AF: 0.00323 AC: 993 AN: 307320 Hom.: 45 Cov.: 0 AF XY: 0.00279 AC XY: 450 AN XY: 161120

African (AFR) AF: 0.103 AC: 712 AN: 6926

American (AMR) AF: 0.00771 AC: 68 AN: 8814

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 9590

East Asian (EAS) AF: 0.00 AC: 0 AN: 18140

South Asian (SAS) AF: 0.000379 AC: 13 AN: 34290

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 20386

Middle Eastern (MID) AF: 0.00219 AC: 3 AN: 1370

European-Non Finnish (NFE) AF: 0.000174 AC: 33 AN: 189510

Other (OTH) AF: 0.00896 AC: 164 AN: 18294

GnomAD4 genome AF: 0.0306 AC: 4657 AN: 152166 Hom.: 255 Cov.: 31 AF XY: 0.0294 AC XY: 2189 AN XY: 74394

African (AFR) AF: 0.107 AC: 4432 AN: 41496

American (AMR) AF: 0.0100 AC: 153 AN: 15296

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5160

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

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10606

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.000221 AC: 15 AN: 67998

Other (OTH) AF: 0.0242 AC: 51 AN: 2110

Alfa AF: 0.0137 Hom.: 37

Bravo AF: 0.0358

Asia WGS AF: 0.00346 AC: 13 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

May 11, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	18
DANN	Benign	0.85
PhyloP100		-0.49
PromoterAI		-0.13	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=298/2	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: rs59211226; hg19: chr3-9975572;