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GeneBe

3-9934531-C-T

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_001077415.3(CRELD1):c.93C>T(p.Pro31=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000476 in 1,614,090 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.00034 ( 1 hom., cov: 32)
Exomes 𝑓: 0.00049 ( 4 hom. )

Consequence

CRELD1
NM_001077415.3 synonymous

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.135
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.67).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 3-9934531-C-T is Benign according to our data. Variant chr3-9934531-C-T is described in ClinVar as [Benign]. Clinvar id is 1615675.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-0.135 with no splicing effect.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High AC in GnomAd at 52 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CRELD1NM_001077415.3 linkuse as main transcriptc.93C>T p.Pro31= synonymous_variant 2/11 ENST00000452070.6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CRELD1ENST00000452070.6 linkuse as main transcriptc.93C>T p.Pro31= synonymous_variant 2/112 NM_001077415.3 P1Q96HD1-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000342
AC:
52
AN:
152172
Hom.:
1
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000655
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00683
Gnomad FIN
AF:
0.0000943
Gnomad MID
AF:
0.00633
Gnomad NFE
AF:
0.000206
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000844
AC:
212
AN:
251152
Hom.:
3
AF XY:
0.00104
AC XY:
141
AN XY:
135838
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000145
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00565
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000264
Gnomad OTH exome
AF:
0.000653
GnomAD4 exome
AF:
0.000490
AC:
716
AN:
1461800
Hom.:
4
Cov.:
33
AF XY:
0.000628
AC XY:
457
AN XY:
727206
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.000134
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00496
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000191
Gnomad4 OTH exome
AF:
0.000828
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000341
AC:
52
AN:
152290
Hom.:
1
Cov.:
32
AF XY:
0.000416
AC XY:
31
AN XY:
74474
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.0000654
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00684
Gnomad4 FIN
AF:
0.0000943
Gnomad4 NFE
AF:
0.000206
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000164
Hom.:
0
Bravo
AF:
0.000117
Asia WGS
AF:
0.000577
AC:
2
AN:
3478
EpiCase
AF:
0.000491
EpiControl
AF:
0.000533

ClinVar

Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

Atrioventricular septal defect, susceptibility to, 2 Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeDec 20, 2023- -
not provided Benign:1
Benign, criteria provided, single submitterclinical testingCeGaT Center for Human Genetics TuebingenAug 01, 2022CRELD1: BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.67
Cadd
Benign
10
Dann
Benign
0.57

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs199599039; hg19: chr3-9976215; COSMIC: COSV55972563; COSMIC: COSV55972563; API