17-80195575-C-T

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001366385.1(CARD14):c.1517C>T(p.Pro506Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0143 in 1,612,032 control chromosomes in the GnomAD database, including 273 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P506R) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.011 ( 16 hom., cov: 33)

Exomes 𝑓: 0.015 ( 257 hom. )

Consequence

CARD14
NM_001366385.1 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.0430

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

Computational evidence support a benign effect (MetaRNN=0.0025039911).

BP6

Variant 17-80195575-C-T is Benign according to our data. Variant chr17-80195575-C-T is described in ClinVar as [Benign]. Clinvar id is 458088.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-80195575-C-T is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0107 (1622/152266) while in subpopulation SAS AF= 0.0455 (219/4812). AF 95% confidence interval is 0.0406. There are 16 homozygotes in gnomad4. There are 763 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1622 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CARD14	NM_001366385.1 link	c.1517C>T	p.Pro506Leu	missense_variant	Exon 14 of 24	ENST00000648509.2	NP_001353314.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CARD14	ENST00000648509.2 link	c.1517C>T	p.Pro506Leu	missense_variant	Exon 14 of 24		NM_001366385.1	ENSP00000498071.1		Q9BXL6-1

Frequencies

GnomAD3 genomes

AF:

0.0107

AC:

1623

AN:

152148

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00374

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00739

Gnomad ASJ

AF:

0.00317

Gnomad EAS

AF:

0.000770

Gnomad SAS

AF:

0.0455

Gnomad FIN

AF:

0.00555

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.0153

Gnomad OTH

AF:

0.00956

GnomAD3 exomes

AF:

0.0137

AC:

3365

AN:

245954

Hom.:

AF XY:

0.0154

AC XY:

2057

AN XY:

133850

show subpopulations

Gnomad AFR exome

AF:

0.00273

Gnomad AMR exome

AF:

0.00545

Gnomad ASJ exome

AF:

0.00455

Gnomad EAS exome

AF:

0.000547

Gnomad SAS exome

AF:

0.0475

Gnomad FIN exome

AF:

0.00559

Gnomad NFE exome

AF:

0.0130

Gnomad OTH exome

AF:

0.0132

GnomAD4 exome

AF:

0.0147

AC:

21460

AN:

1459766

Hom.:

257

Cov.:

AF XY:

0.0155

AC XY:

11249

AN XY:

726174

show subpopulations

Gnomad4 AFR exome

AF:

0.00341

Gnomad4 AMR exome

AF:

0.00576

Gnomad4 ASJ exome

AF:

0.00421

Gnomad4 EAS exome

AF:

0.000403

Gnomad4 SAS exome

AF:

0.0441

Gnomad4 FIN exome

AF:

0.00624

Gnomad4 NFE exome

AF:

0.0143

Gnomad4 OTH exome

AF:

0.0146

GnomAD4 genome

AF:

0.0107

AC:

1622

AN:

152266

Hom.:

Cov.:

AF XY:

0.0102

AC XY:

763

AN XY:

74452

show subpopulations

Gnomad4 AFR

AF:

0.00371

Gnomad4 AMR

AF:

0.00738

Gnomad4 ASJ

AF:

0.00317

Gnomad4 EAS

AF:

0.000772

Gnomad4 SAS

AF:

0.0455

Gnomad4 FIN

AF:

0.00555

Gnomad4 NFE

AF:

0.0153

Gnomad4 OTH

AF:

0.00946

Alfa

AF:

0.0126

Hom.:

Bravo

AF:

0.00911

TwinsUK

AF:

0.0143

AC:

ALSPAC

AF:

0.0122

AC:

ESP6500AA

AF:

0.00340

AC:

ESP6500EA

AF:

0.0169

AC:

145

ExAC

AF:

0.0144

AC:

1752

Asia WGS

AF:

0.0280

AC:

AN:

3478

EpiCase

AF:

0.0142

EpiControl

AF:

0.0107

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Pityriasis rubra pilaris;C1864497:Psoriasis 2

Benign:1

Feb 02, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Autoinflammatory syndrome

Benign:1

Jan 29, 2022

Genome Diagnostics Laboratory, The Hospital for Sick Children

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.060

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.61

CADD

Benign

0.73

DANN

Benign

0.63

DEOGEN2

Benign

0.0045

T;T;.;T

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.0037

LIST_S2

Benign

0.44

.;.;T;T

MetaRNN

Benign

0.0025

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-1.3

N;N;N;N

PrimateAI

Benign

0.29

PROVEAN

Benign

-0.72

.;.;.;N

REVEL

Benign

0.046

Sift

Benign

0.12

.;.;.;T

Sift4G

Benign

0.38

T;.;T;T

Polyphen

0.0

B;B;.;B

Vest4

0.034

MPC

0.15

ClinPred

0.0013

GERP RS

1.4

Varity_R

0.027

gMVP

0.12

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