rs76764016

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_001077415.3(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_001077415.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -3.06

Publications

9 publications found

Variant links:

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 links:

ENSG00000288550 (HGNC:):

ENSG00000288550 links:

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

PRRT3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CRELD1	NM_001077415.3 link	c.945G>A	p.Pro315Pro	synonymous_variant	Exon 10 of 11	ENST00000452070.6	NP_001070883.2	Q96HD1-1A0A024R2G1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CRELD1	ENST00000452070.6 link	c.945G>A	p.Pro315Pro	synonymous_variant	Exon 10 of 11	2	NM_001077415.3	ENSP00000393643.2	Q96HD1-1
ENSG00000288550	ENST00000683484.1 link	n.*593G>A		non_coding_transcript_exon_variant	Exon 23 of 24			ENSP00000507040.1	A0A804HIF2
ENSG00000288550	ENST00000683484.1 link	n.*593G>A		3_prime_UTR_variant	Exon 23 of 24			ENSP00000507040.1	A0A804HIF2

Frequencies

GnomAD3 genomes

AF:

0.0108

AC:

1644

AN:

152050

Hom.:

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.0141

AC XY:

10222

AN XY:

727220

show subpopulations

African (AFR)

AF:

0.00233

AC:

AN:

33480

American (AMR)

AF:

0.00353

AC:

158

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00199

AC:

AN:

26134

East Asian (EAS)

AF:

0.0000504

AC:

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:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0168

AC:

18668

AN:

1111998

Other (OTH)

AF:

0.0116

AC:

701

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

1320

2640

3961

5281

6601

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

686

1372

2058

2744

3430

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0108

AC:

1644

AN:

152168

Hom.:

Cov.:

AF XY:

0.0100

AC XY:

746

AN XY:

74378

show subpopulations

African (AFR)

AF:

0.00303

AC:

126

AN:

41522

American (AMR)

AF:

0.00556

AC:

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.00202

AC:

AN:

3472

East Asian (EAS)

AF:

0.000584

AC:

AN:

5140

South Asian (SAS)

AF:

0.00291

AC:

AN:

4816

European-Finnish (FIN)

AF:

0.0161

AC:

171

AN:

10602

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0173

AC:

1176

AN:

68000

Other (OTH)

AF:

0.00994

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

157

236

314

393

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0140

Hom.:

Bravo

AF:

0.00974

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.0149

EpiControl

AF:

0.0141

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Apr 22, 2014

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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

Jan 27, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

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

-0.61

CADD

Benign

0.076

(source)

DANN

Benign

0.88

PhyloP100

-3.1

RBP_binding_hub_radar

1.1

RBP_regulation_power_radar

2.8

Mutation Taster

=99/1

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over