Variant 22-37491799-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000251973.10(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 Benign (★★).

Frequency

Genomes: 𝑓 0.0084 ( 5 hom., cov: 27)

Exomes 𝑓: 0.0093 ( 93 hom. )

Consequence

CARD10
ENST00000251973.10 synonymous

Scores

Clinical Significance

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

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]

CARD10 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.48).

BP6

Variant 22-37491799-G-A is Benign according to our data. Variant chr22-37491799-G-A is described in ClinVar as [Benign]. Clinvar id is 716133.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.426 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CARD10	NM_014550.4 linkuse as main transcript	c.2820C>T	p.Ile940=	synonymous_variant	19/20	ENST00000251973.10	NP_055365.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CARD10	ENST00000251973.10 linkuse as main transcript	c.2820C>T	p.Ile940=	synonymous_variant	19/20	1	NM_014550.4	ENSP00000251973	P1	Q9BWT7-1

Frequencies

GnomAD3 genomes

AF:

0.00837

AC:

1200

AN:

143334

Hom.:

Cov.:

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.:

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.:

Cov.:

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

AF:

0.00836

AC:

1200

AN:

143480

Hom.:

Cov.:

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.:

Bravo

AF:

0.00524

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.0106

EpiControl

AF:

0.00848

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

CARD10-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Apr 04, 2019

This 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). -

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over