3-9940633-A-G

Position:

• chr3-9940633-A-G

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.461-217A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.072 in 148,600 control chromosomes in the GnomAD database, including 1,170 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.072 (1170 hom., cov: 27)
• 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]

PRRT3 (HGNC:26591): (proline rich transmembrane protein 3) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BP6: Variant 3-9940633-A-G is Benign according to our data. Variant chr3-9940633-A-G is described in ClinVar as [Benign]. Clinvar id is 1282127.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.236 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CRELD1	NM_001077415.3	c.461-217A>G		intron_variant		ENST00000452070.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CRELD1	ENST00000452070.6	c.461-217A>G		intron_variant		2	NM_001077415.3	P1

Frequencies

GnomAD3 genomes AF: 0.0719 AC: 10670 AN: 148486 Hom.: 1167 Cov.: 27

Gnomad AFR AF: 0.240

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0331

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0239

Gnomad SAS AF: 0.0473

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0318

Gnomad NFE AF: 0.00104

Gnomad OTH AF: 0.0573

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0720 AC: 10700 AN: 148600 Hom.: 1170 Cov.: 27 AF XY: 0.0702 AC XY: 5084 AN XY: 72424

Gnomad4 AFR AF: 0.240

Gnomad4 AMR AF: 0.0332

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.0240

Gnomad4 SAS AF: 0.0470

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00104

Gnomad4 OTH AF: 0.0586

Alfa AF: 0.00276 Hom.: 5

Bravo AF: 0.0840

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

Nov 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.0
DANN	Benign	0.24

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs375279562; hg19: chr3-9982317;