rs139789664

Positions:

• chr17-80205132-C-T

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BS1 BS2

The NM_001366385.1(CARD14):​c.2496C>T​(p.Leu832=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00516 in 1,613,754 control chromosomes in the GnomAD database, including 26 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0048 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0052 (25 hom.)
• Consequence: CARD14 NM_001366385.1 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.520

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.38).
• BP6: Variant 17-80205132-C-T is Benign according to our data. Variant chr17-80205132-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 527887.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-80205132-C-T is described in Lovd as [Likely_benign].
• BP7: Synonymous conserved (PhyloP=-0.52 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00482 (734/152306) while in subpopulation NFE AF= 0.00601 (409/68028). AF 95% confidence interval is 0.00553. There are 1 homozygotes in gnomad4. There are 315 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 734 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CARD14	NM_001366385.1	c.2496C>T	p.Leu832=	synonymous_variant	21/24	ENST00000648509.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CARD14	ENST00000648509.2	c.2496C>T	p.Leu832=	synonymous_variant	21/24		NM_001366385.1	P1

Frequencies

GnomAD3 genomes AF: 0.00482 AC: 734 AN: 152188 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00463

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00485

Gnomad ASJ AF: 0.00432

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00235

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00603

Gnomad OTH AF: 0.00718

GnomAD3 exomes AF: 0.00376 AC: 942 AN: 250232 Hom.: 1 AF XY: 0.00356 AC XY: 482 AN XY: 135534

Gnomad AFR exome AF: 0.00352

Gnomad AMR exome AF: 0.00316

Gnomad ASJ exome AF: 0.00439

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00101

Gnomad FIN exome AF: 0.00242

Gnomad NFE exome AF: 0.00560

Gnomad OTH exome AF: 0.00279

GnomAD4 exome AF: 0.00520 AC: 7593 AN: 1461448 Hom.: 25 Cov.: 35 AF XY: 0.00506 AC XY: 3680 AN XY: 727066

Gnomad4 AFR exome AF: 0.00332

Gnomad4 AMR exome AF: 0.00353

Gnomad4 ASJ exome AF: 0.00452

Gnomad4 EAS exome AF: 0.0000504

Gnomad4 SAS exome AF: 0.000997

Gnomad4 FIN exome AF: 0.00269

Gnomad4 NFE exome AF: 0.00602

Gnomad4 OTH exome AF: 0.00467

GnomAD4 genome AF: 0.00482 AC: 734 AN: 152306 Hom.: 1 Cov.: 32 AF XY: 0.00423 AC XY: 315 AN XY: 74478

Gnomad4 AFR AF: 0.00464

Gnomad4 AMR AF: 0.00484

Gnomad4 ASJ AF: 0.00432

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000622

Gnomad4 FIN AF: 0.00235

Gnomad4 NFE AF: 0.00601

Gnomad4 OTH AF: 0.00711

Alfa AF: 0.00529 Hom.: 1

Bravo AF: 0.00486

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.00502

EpiControl AF: 0.00522

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Likely benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -
Likely benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Feb 01, 2024	CARD14: BP4, BP7 -

Pityriasis rubra pilaris;C1864497:Psoriasis 2 Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 29, 2024

- -

Autoinflammatory syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome Diagnostics Laboratory, The Hospital for Sick Children

May 03, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.38
CADD	Benign	2.4
DANN	Benign	0.91

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

Other links and lift over

dbSNP: rs139789664; hg19: chr17-78178931; COSMIC: COSV100413290; COSMIC: COSV100413290;