rs76764016

Positions:

• chr3-9943412-G-A
• chr3-9943412-G-C
• chr3-9943412-G-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_001077415.3(CRELD1):​c.945G>A​(p.Pro315=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.014 in 1,613,998 control chromosomes in the GnomAD database, including 193 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.011 (13 hom., cov: 32)
  • Exomes 𝑓: 0.014 (180 hom.)
• Consequence: CRELD1 NM_001077415.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -3.06

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:):

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

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).
• BP6: Variant 3-9943412-G-A is Benign according to our data. Variant chr3-9943412-G-A is described in ClinVar as [Benign]. Clinvar id is 137029.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-9943412-G-A is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=-3.06 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0108 (1644/152168) while in subpopulation NFE AF= 0.0173 (1176/68000). AF 95% confidence interval is 0.0165. There are 13 homozygotes in gnomad4. There are 746 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 1644 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CRELD1	NM_001077415.3	c.945G>A	p.Pro315=	synonymous_variant	10/11	ENST00000452070.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CRELD1	ENST00000452070.6	c.945G>A	p.Pro315=	synonymous_variant	10/11	2	NM_001077415.3	P1

Frequencies

GnomAD3 genomes AF: 0.0108 AC: 1644 AN: 152050 Hom.: 13 Cov.: 32

Gnomad AFR AF: 0.00304

Gnomad AMI AF: 0.0439

Gnomad AMR AF: 0.00556

Gnomad ASJ AF: 0.00202

Gnomad EAS AF: 0.000582

Gnomad SAS AF: 0.00290

Gnomad FIN AF: 0.0161

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0173

Gnomad OTH AF: 0.0100

GnomAD3 exomes AF: 0.0109 AC: 2735 AN: 251330 Hom.: 17 AF XY: 0.0114 AC XY: 1545 AN XY: 135870

Gnomad AFR exome AF: 0.00289

Gnomad AMR exome AF: 0.00359

Gnomad ASJ exome AF: 0.00129

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.00431

Gnomad FIN exome AF: 0.0156

Gnomad NFE exome AF: 0.0179

Gnomad OTH exome AF: 0.00798

GnomAD4 exome AF: 0.0143 AC: 20922 AN: 1461830 Hom.: 180 Cov.: 33 AF XY: 0.0141 AC XY: 10222 AN XY: 727220

Gnomad4 AFR exome AF: 0.00233

Gnomad4 AMR exome AF: 0.00353

Gnomad4 ASJ exome AF: 0.00199

Gnomad4 EAS exome AF: 0.0000504

Gnomad4 SAS exome AF: 0.00390

Gnomad4 FIN exome AF: 0.0170

Gnomad4 NFE exome AF: 0.0168

Gnomad4 OTH exome AF: 0.0116

GnomAD4 genome AF: 0.0108 AC: 1644 AN: 152168 Hom.: 13 Cov.: 32 AF XY: 0.0100 AC XY: 746 AN XY: 74378

Gnomad4 AFR AF: 0.00303

Gnomad4 AMR AF: 0.00556

Gnomad4 ASJ AF: 0.00202

Gnomad4 EAS AF: 0.000584

Gnomad4 SAS AF: 0.00291

Gnomad4 FIN AF: 0.0161

Gnomad4 NFE AF: 0.0173

Gnomad4 OTH AF: 0.00994

Alfa AF: 0.0110 Hom.: 5

Bravo AF: 0.00974

Asia WGS AF: 0.00115 AC: 4 AN: 3478

EpiCase AF: 0.0149

EpiControl AF: 0.0141

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Apr 22, 2014

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Atrioventricular septal defect, susceptibility to, 2 Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 18, 2023

- -

not provided Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	0.076
DANN	Benign	0.88
RBP_binding_hub_radar		1.1
RBP_regulation_power_radar		2.8

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: rs76764016; hg19: chr3-9985096;