Variant 17-80191403-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_001366385.1(CARD14):c.1170C>T(p.Phe390=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0424 in 1,613,730 control chromosomes in the GnomAD database, including 1,633 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.035 ( 119 hom., cov: 33)

Exomes 𝑓: 0.043 ( 1514 hom. )

Consequence

CARD14
NM_001366385.1 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -3.15

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.47).

BP6

Variant 17-80191403-C-T is Benign according to our data. Variant chr17-80191403-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 458084.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-3.15 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0355 (5404/152270) while in subpopulation NFE AF= 0.0462 (3144/68004). AF 95% confidence interval is 0.0449. There are 119 homozygotes in gnomad4. There are 2582 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 5404 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CARD14	NM_001366385.1 linkuse as main transcript	c.1170C>T	p.Phe390=	synonymous_variant	11/24	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.1170C>T	p.Phe390=	synonymous_variant	11/24		NM_001366385.1	ENSP00000498071	P1	Q9BXL6-1

Frequencies

GnomAD3 genomes

AF:

0.0355

AC:

5397

AN:

152152

Hom.:

120

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0243

Gnomad AMI

AF:

0.0143

Gnomad AMR

AF:

0.0308

Gnomad ASJ

AF:

0.0291

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0344

Gnomad FIN

AF:

0.0391

Gnomad MID

AF:

0.0285

Gnomad NFE

AF:

0.0462

Gnomad OTH

AF:

0.0339

GnomAD3 exomes

AF:

0.0350

AC:

8785

AN:

250654

Hom.:

171

AF XY:

0.0356

AC XY:

4832

AN XY:

135638

show subpopulations

Gnomad AFR exome

AF:

0.0245

Gnomad AMR exome

AF:

0.0187

Gnomad ASJ exome

AF:

0.0367

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0326

Gnomad FIN exome

AF:

0.0375

Gnomad NFE exome

AF:

0.0473

Gnomad OTH exome

AF:

0.0362

GnomAD4 exome

AF:

0.0431

AC:

63035

AN:

1461460

Hom.:

1514

Cov.:

AF XY:

0.0428

AC XY:

31127

AN XY:

727048

show subpopulations

Gnomad4 AFR exome

AF:

0.0256

Gnomad4 AMR exome

AF:

0.0201

Gnomad4 ASJ exome

AF:

0.0346

Gnomad4 EAS exome

AF:

0.000126

Gnomad4 SAS exome

AF:

0.0338

Gnomad4 FIN exome

AF:

0.0382

Gnomad4 NFE exome

AF:

0.0475

Gnomad4 OTH exome

AF:

0.0386

GnomAD4 genome

AF:

0.0355

AC:

5404

AN:

152270

Hom.:

119

Cov.:

AF XY:

0.0347

AC XY:

2582

AN XY:

74450

show subpopulations

Gnomad4 AFR

AF:

0.0245

Gnomad4 AMR

AF:

0.0308

Gnomad4 ASJ

AF:

0.0291

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0338

Gnomad4 FIN

AF:

0.0391

Gnomad4 NFE

AF:

0.0462

Gnomad4 OTH

AF:

0.0336

Alfa

AF:

0.0400

Hom.:

Bravo

AF:

0.0344

Asia WGS

AF:

0.0170

AC:

AN:

3478

EpiCase

AF:

0.0452

EpiControl

AF:

0.0495

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 09, 2018	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Pityriasis rubra pilaris;C1864497:Psoriasis 2

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Autoinflammatory syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome Diagnostics Laboratory, The Hospital for Sick Children

Jan 22, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.47

CADD

Benign

0.84

DANN

Benign

0.93

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