Variant chr17-80181383-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001366385.1(CARD14):c.-20-36A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.542 in 1,495,346 control chromosomes in the GnomAD database, including 224,182 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). There are indicators that this mutation may affect the branch point..

Frequency

Genomes: 𝑓 0.59 ( 28239 hom., cov: 32)

Exomes 𝑓: 0.54 ( 195943 hom. )

Consequence

CARD14
NM_001366385.1 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.239

Variant links:

Genes affected

CARD14 (HGNC:16446): (caspase recruitment domain family member 14) This gene encodes a caspase recruitment domain-containing protein that is a member of the membrane-associated guanylate kinase (MAGUK) family of proteins. Members of this protein family are scaffold proteins that are involved in a diverse array of cellular processes including cellular adhesion, signal transduction and cell polarity control. This protein has been shown to specifically interact with BCL10, a protein known to function as a positive regulator of cell apoptosis and NF-kappaB activation. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Apr 2012]

CARD14 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

This place is a probable branch point but likely benign (scored 1 / 10). Computational evidence support a benign effect (BayesDel_noAF=-1.0).

BP6

Variant 17-80181383-A-C is Benign according to our data. Variant chr17-80181383-A-C is described in ClinVar as [Benign]. Clinvar id is 1260535.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.773 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CARD14	NM_001366385.1 linkuse as main transcript	c.-20-36A>C		intron_variant		ENST00000648509.2	NP_001353314.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CARD14	ENST00000648509.2 linkuse as main transcript	c.-20-36A>C		intron_variant			NM_001366385.1	ENSP00000498071	P1	Q9BXL6-1

Frequencies

GnomAD3 genomes

AF:

0.595

AC:

90379

AN:

151950

Hom.:

28199

Cov.:

show subpopulations

Gnomad AFR

AF:

0.779

Gnomad AMI

AF:

0.496

Gnomad AMR

AF:

0.424

Gnomad ASJ

AF:

0.554

Gnomad EAS

AF:

0.652

Gnomad SAS

AF:

0.609

Gnomad FIN

AF:

0.603

Gnomad MID

AF:

0.551

Gnomad NFE

AF:

0.519

Gnomad OTH

AF:

0.552

GnomAD4 exome

AF:

0.536

AC:

719992

AN:

1343278

Hom.:

195943

Cov.:

AF XY:

0.537

AC XY:

355163

AN XY:

661014

show subpopulations

Gnomad4 AFR exome

AF:

0.793

Gnomad4 AMR exome

AF:

0.363

Gnomad4 ASJ exome

AF:

0.557

Gnomad4 EAS exome

AF:

0.697

Gnomad4 SAS exome

AF:

0.593

Gnomad4 FIN exome

AF:

0.591

Gnomad4 NFE exome

AF:

0.521

Gnomad4 OTH exome

AF:

0.546

GnomAD4 genome

AF:

0.595

AC:

90471

AN:

152068

Hom.:

28239

Cov.:

AF XY:

0.594

AC XY:

44159

AN XY:

74340

show subpopulations

Gnomad4 AFR

AF:

0.780

Gnomad4 AMR

AF:

0.424

Gnomad4 ASJ

AF:

0.554

Gnomad4 EAS

AF:

0.652

Gnomad4 SAS

AF:

0.610

Gnomad4 FIN

AF:

0.603

Gnomad4 NFE

AF:

0.519

Gnomad4 OTH

AF:

0.553

Alfa

AF:

0.431

Hom.:

1215

Bravo

AF:

0.589

Asia WGS

AF:

0.621

AC:

2159

AN:

3478

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	GeneDx	Jul 09, 2018	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Nov 12, 2023

This variant is classified as Benign based on local population frequency. This variant was detected in 64% of patients studied by a panel of primary immunodeficiencies. Number of patients: 61. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

1.0

DANN

Benign

0.47

BranchPoint Hunter

1.0

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

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