rs76764016

Variant names:

• chr3-9943412-G-A
• rs76764016
• NM_001077415.3:c.945G>A

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_001374317.1(CRELD1):​c.945G>A​(p.Pro315Pro) 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_001374317.1 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -3.06
• Publications: 9 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]

ENSG00000288550 (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

Our verdict: Benign. The variant received -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 VariationId is 137029.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• 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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 13 AD,AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001374317.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CRELD1	NM_001077415.3	MANE Select	c.945G>A	p.Pro315Pro	synonymous	Exon 10 of 11	NP_001070883.2
	CRELD1	NM_001374317.1		c.945G>A	p.Pro315Pro	synonymous	Exon 10 of 12	NP_001361246.1
	CRELD1	NM_001374318.1		c.945G>A	p.Pro315Pro	synonymous	Exon 9 of 11	NP_001361247.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CRELD1	ENST00000452070.6	TSL:2 MANE Select	c.945G>A	p.Pro315Pro	synonymous	Exon 10 of 11	ENSP00000393643.2
	CRELD1	ENST00000326434.9	TSL:1	c.945G>A	p.Pro315Pro	synonymous	Exon 10 of 12	ENSP00000321856.5
	CRELD1	ENST00000383811.8	TSL:1	c.945G>A	p.Pro315Pro	synonymous	Exon 9 of 10	ENSP00000373322.3

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

GnomAD2 exomes AF: 0.0109 AC: 2735 AN: 251330 AF XY: 0.0114

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 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

African (AFR) AF: 0.00233 AC: 78 AN: 33480

American (AMR) AF: 0.00353 AC: 158 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00199 AC: 52 AN: 26134

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39700

South Asian (SAS) AF: 0.00390 AC: 336 AN: 86256

European-Finnish (FIN) AF: 0.0170 AC: 909 AN: 53376

Middle Eastern (MID) AF: 0.00312 AC: 18 AN: 5768

European-Non Finnish (NFE) AF: 0.0168 AC: 18668 AN: 1111998

Other (OTH) AF: 0.0116 AC: 701 AN: 60396

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

African (AFR) AF: 0.00303 AC: 126 AN: 41522

American (AMR) AF: 0.00556 AC: 85 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00202 AC: 7 AN: 3472

East Asian (EAS) AF: 0.000584 AC: 3 AN: 5140

South Asian (SAS) AF: 0.00291 AC: 14 AN: 4816

European-Finnish (FIN) AF: 0.0161 AC: 171 AN: 10602

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

European-Non Finnish (NFE) AF: 0.0173 AC: 1176 AN: 68000

Other (OTH) AF: 0.00994 AC: 21 AN: 2112

Alfa AF: 0.0140 Hom.: 36

Bravo AF: 0.00974

Asia WGS AF: 0.00115 AC: 4 AN: 3478

EpiCase AF: 0.0149

EpiControl AF: 0.0141

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Atrioventricular septal defect, susceptibility to, 2 (1)
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	0.076
DANN	Benign	0.88
PhyloP100		-3.1
RBP_binding_hub_radar		1.1
RBP_regulation_power_radar		2.8
Mutation Taster		=99/1	polymorphism

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: rs76764016; hg19: chr3-9985096;