rs139717648

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS1

The NM_001374317.1(CRELD1):c.1172C>T(p.Thr391Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000538 in 930,388 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0021 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00022 ( 1 hom. )

Consequence

CRELD1
NM_001374317.1 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.349

Publications

1 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 -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0037197173).

BP6

Variant 3-9944013-C-T is Benign according to our data. Variant chr3-9944013-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 534232.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00214 (326/152330) while in subpopulation AFR AF = 0.00751 (312/41560). AF 95% confidence interval is 0.00682. There are 0 homozygotes in GnomAd4. There are 154 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CRELD1	NM_001077415.3	MANE Select	c.1049-352C>T		intron	N/A	NP_001070883.2	Q96HD1-1
CRELD1	NM_001374317.1		c.1172C>T	p.Thr391Ile	missense	Exon 11 of 12	NP_001361246.1	A0A804HJJ0
CRELD1	NM_001374318.1		c.1172C>T	p.Thr391Ile	missense	Exon 10 of 11	NP_001361247.1	A0A804HJJ0

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CRELD1	ENST00000326434.9	TSL:1	c.1160C>T	p.Thr387Ile	missense	Exon 11 of 12	ENSP00000321856.5	Q96HD1-2
CRELD1	ENST00000452070.6	TSL:2 MANE Select	c.1049-352C>T		intron	N/A	ENSP00000393643.2	Q96HD1-1
CRELD1	ENST00000383811.8	TSL:1	c.1049-352C>T		intron	N/A	ENSP00000373322.3	Q96HD1-1

Frequencies

GnomAD3 genomes

AF:

0.00214

AC:

326

AN:

152212

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00753

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000458

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00191

GnomAD2 exomes

AF:

0.000546

AC:

136

AN:

249050

AF XY:

0.000371

show subpopulations

Gnomad AFR exome

AF:

0.00794

Gnomad AMR exome

AF:

0.000173

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000225

AC:

175

AN:

778058

Hom.:

Cov.:

AF XY:

0.000164

AC XY:

AN XY:

413748

show subpopulations

African (AFR)

AF:

0.00719

AC:

148

AN:

20578

American (AMR)

AF:

0.000273

AC:

AN:

43882

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

21902

East Asian (EAS)

AF:

0.00

AC:

AN:

36618

South Asian (SAS)

AF:

0.00

AC:

AN:

72776

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53188

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4444

European-Non Finnish (NFE)

AF:

0.00000205

AC:

AN:

486764

Other (OTH)

AF:

0.000369

AC:

AN:

37906

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.00214

AC:

326

AN:

152330

Hom.:

Cov.:

AF XY:

0.00207

AC XY:

154

AN XY:

74490

show subpopulations

African (AFR)

AF:

0.00751

AC:

312

AN:

41560

American (AMR)

AF:

0.000457

AC:

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68034

Other (OTH)

AF:

0.00189

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.511

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.000919

Hom.:

Bravo

AF:

0.00238

ESP6500AA

AF:

0.00953

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000692

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Atrioventricular septal defect, susceptibility to, 2 (1)

CRELD1-related disorder (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.072

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.58

CADD

Benign

(source)

DANN

Uncertain

0.98

Eigen

Benign

-0.78

Eigen_PC

Benign

-0.84

FATHMM_MKL

Benign

0.051

LIST_S2

Benign

0.43

M_CAP

Benign

0.052

MetaRNN

Benign

0.0037

MetaSVM

Benign

-1.1

PhyloP100

0.35

PrimateAI

Benign

0.29

PROVEAN

Benign

0.81

REVEL

Benign

0.085

Sift

Benign

0.042

Sift4G

Benign

0.078

Polyphen

0.0050

Vest4

0.18

MVP

0.40

MPC

0.70

ClinPred

0.037

GERP RS

2.6

gMVP

0.42

Mutation Taster

=96/4

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over