3-9934334-G-T

Variant names:

• chr3-9934334-G-T
• rs57022843
• ENST00000383811.8:c.-105G>T

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.-19-86G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0163 in 1,077,832 control chromosomes in the GnomAD database, including 1,028 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.051 (577 hom., cov: 31)
  • Exomes 𝑓: 0.011 (451 hom.)
• Consequence: CRELD1 NM_001077415.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.475
• 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 3-9934334-G-T is Benign according to our data. Variant chr3-9934334-G-T is described in ClinVar as [Benign]. Clinvar id is 1275722.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.162 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CRELD1	NM_001077415.3	c.-19-86G>T		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.-19-86G>T		intron_variant	Intron 1 of 10	2	NM_001077415.3	ENSP00000393643.2
ENSG00000288550	ENST00000683484.1	n.1400-501G>T		intron_variant	Intron 16 of 23			ENSP00000507040.1

Frequencies

GnomAD3 genomes AF: 0.0509 AC: 7729 AN: 151740 Hom.: 575 Cov.: 31

Gnomad AFR AF: 0.166

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0268

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0213

Gnomad SAS AF: 0.0477

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.000824

Gnomad OTH AF: 0.0404

GnomAD4 exome AF: 0.0106 AC: 9854 AN: 925974 Hom.: 451 Cov.: 12 AF XY: 0.0110 AC XY: 5273 AN XY: 481024

African (AFR) AF: 0.171 AC: 3912 AN: 22902

American (AMR) AF: 0.0304 AC: 1311 AN: 43056

Ashkenazi Jewish (ASJ) AF: 0.0000441 AC: 1 AN: 22656

East Asian (EAS) AF: 0.0179 AC: 664 AN: 37002

South Asian (SAS) AF: 0.0390 AC: 2924 AN: 75010

European-Finnish (FIN) AF: 0.000217 AC: 10 AN: 46146

Middle Eastern (MID) AF: 0.00994 AC: 33 AN: 3320

European-Non Finnish (NFE) AF: 0.000558 AC: 353 AN: 633174

Other (OTH) AF: 0.0151 AC: 646 AN: 42708

GnomAD4 genome AF: 0.0510 AC: 7743 AN: 151858 Hom.: 577 Cov.: 31 AF XY: 0.0496 AC XY: 3680 AN XY: 74218

African (AFR) AF: 0.166 AC: 6849 AN: 41352

American (AMR) AF: 0.0269 AC: 411 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.0213 AC: 110 AN: 5154

South Asian (SAS) AF: 0.0475 AC: 227 AN: 4780

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10564

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.000824 AC: 56 AN: 67968

Other (OTH) AF: 0.0400 AC: 84 AN: 2100

Alfa AF: 0.0127 Hom.: 38

Bravo AF: 0.0587

Asia WGS AF: 0.0290 AC: 101 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

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	-0.85
CADD	Benign	10
DANN	Benign	0.72
PhyloP100		0.47
PromoterAI		-0.066	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=300/0	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: rs57022843; hg19: chr3-9976018;