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GeneBe

22-37491799-G-A

Variant summary

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

The NM_014550.4(CARD10):c.2820C>T(p.Ile940=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00922 in 1,465,622 control chromosomes in the GnomAD database, including 98 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0084 ( 5 hom., cov: 27)
Exomes 𝑓: 0.0093 ( 93 hom. )

Consequence

CARD10
NM_014550.4 synonymous

Scores

2

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.426
Variant links:
Genes affected
CARD10 (HGNC:16422): (caspase recruitment domain family member 10) The caspase recruitment domain (CARD) is a protein module that consists of 6 or 7 antiparallel alpha helices. It participates in apoptosis signaling through highly specific protein-protein homophilic interactions. Like several other CARD proteins, CARD10 belongs to the membrane-associated guanylate kinase (MAGUK) family and activates NF-kappa-B (NFKB; see MIM 164011) through BCL10 (MIM 603517) (Wang et al., 2001 [PubMed 11259443]).[supplied by OMIM, Mar 2008]

Genome browser will be placed here

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=-0.48).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 22-37491799-G-A is Benign according to our data. Variant chr22-37491799-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 716133.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=-0.426 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 Homozygotes in GnomAd at 5 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CARD10NM_014550.4 linkuse as main transcriptc.2820C>T p.Ile940= synonymous_variant 19/20 ENST00000251973.10

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CARD10ENST00000251973.10 linkuse as main transcriptc.2820C>T p.Ile940= synonymous_variant 19/201 NM_014550.4 P1Q9BWT7-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00837
AC:
1200
AN:
143334
Hom.:
5
Cov.:
27
show subpopulations
Gnomad AFR
AF:
0.00180
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00421
Gnomad ASJ
AF:
0.00357
Gnomad EAS
AF:
0.000236
Gnomad SAS
AF:
0.00273
Gnomad FIN
AF:
0.0413
Gnomad MID
AF:
0.00654
Gnomad NFE
AF:
0.00998
Gnomad OTH
AF:
0.00598
GnomAD3 exomes
AF:
0.00805
AC:
2008
AN:
249408
Hom.:
13
AF XY:
0.00819
AC XY:
1107
AN XY:
135150
show subpopulations
Gnomad AFR exome
AF:
0.00117
Gnomad AMR exome
AF:
0.00266
Gnomad ASJ exome
AF:
0.00199
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00366
Gnomad FIN exome
AF:
0.0332
Gnomad NFE exome
AF:
0.00897
Gnomad OTH exome
AF:
0.0115
GnomAD4 exome
AF:
0.00931
AC:
12308
AN:
1322142
Hom.:
93
Cov.:
33
AF XY:
0.00934
AC XY:
6129
AN XY:
656326
show subpopulations
Gnomad4 AFR exome
AF:
0.00115
Gnomad4 AMR exome
AF:
0.00282
Gnomad4 ASJ exome
AF:
0.00377
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00373
Gnomad4 FIN exome
AF:
0.0429
Gnomad4 NFE exome
AF:
0.00929
Gnomad4 OTH exome
AF:
0.00985
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00836
AC:
1200
AN:
143480
Hom.:
5
Cov.:
27
AF XY:
0.00925
AC XY:
644
AN XY:
69654
show subpopulations
Gnomad4 AFR
AF:
0.00180
Gnomad4 AMR
AF:
0.00420
Gnomad4 ASJ
AF:
0.00357
Gnomad4 EAS
AF:
0.000236
Gnomad4 SAS
AF:
0.00272
Gnomad4 FIN
AF:
0.0413
Gnomad4 NFE
AF:
0.00998
Gnomad4 OTH
AF:
0.00592
Alfa
AF:
0.00662
Hom.:
1
Bravo
AF:
0.00524
Asia WGS
AF:
0.000866
AC:
3
AN:
3478
EpiCase
AF:
0.0106
EpiControl
AF:
0.00848

ClinVar

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

Submissions by phenotype

CARD10-related disorder Benign:1
Likely benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact SciencesApr 04, 2019This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -
not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeDec 31, 2019- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.48
Cadd
Benign
6.0
Dann
Benign
0.81

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

LitVar

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

Other links and lift over

dbSNP: rs55875977; hg19: chr22-37887806; COSMIC: COSV99325463; COSMIC: COSV99325463; API