chr17-80188371-G-A

Position:

chr17-80188371-G-A

Variant summary

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

The NM_001366385.1(CARD14):c.676-6G>A variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.339 in 1,604,012 control chromosomes in the GnomAD database, including 94,043 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.31 ( 7599 hom., cov: 32)

Exomes 𝑓: 0.34 ( 86444 hom. )

Consequence

CARD14
NM_001366385.1 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.0001668

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6O:1

Conservation

PhyloP100: 0.0180

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 (BayesDel_noAF=-0.85).

BP6

Variant 17-80188371-G-A is Benign according to our data. Variant chr17-80188371-G-A is described in ClinVar as [Benign]. Clinvar id is 402484.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-80188371-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.385 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CARD14	NM_001366385.1 linkuse as main transcript	c.676-6G>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000648509.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CARD14	ENST00000648509.2 linkuse as main transcript	c.676-6G>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant			NM_001366385.1	P1	Q9BXL6-1

Frequencies

GnomAD3 genomes

AF:

0.306

AC:

46494

AN:

151920

Hom.:

7596

Cov.:

show subpopulations

Gnomad AFR

AF:

0.202

Gnomad AMI

AF:

0.410

Gnomad AMR

AF:

0.275

Gnomad ASJ

AF:

0.407

Gnomad EAS

AF:

0.399

Gnomad SAS

AF:

0.295

Gnomad FIN

AF:

0.405

Gnomad MID

AF:

0.402

Gnomad NFE

AF:

0.347

Gnomad OTH

AF:

0.315

GnomAD3 exomes

AF:

0.329

AC:

79366

AN:

240926

Hom.:

13535

AF XY:

0.335

AC XY:

43642

AN XY:

130436

show subpopulations

Gnomad AFR exome

AF:

0.198

Gnomad AMR exome

AF:

0.260

Gnomad ASJ exome

AF:

0.409

Gnomad EAS exome

AF:

0.400

Gnomad SAS exome

AF:

0.287

Gnomad FIN exome

AF:

0.394

Gnomad NFE exome

AF:

0.348

Gnomad OTH exome

AF:

0.340

GnomAD4 exome

AF:

0.343

AC:

497387

AN:

1451972

Hom.:

86444

Cov.:

AF XY:

0.342

AC XY:

247135

AN XY:

722104

show subpopulations

Gnomad4 AFR exome

AF:

0.200

Gnomad4 AMR exome

AF:

0.263

Gnomad4 ASJ exome

AF:

0.415

Gnomad4 EAS exome

AF:

0.427

Gnomad4 SAS exome

AF:

0.287

Gnomad4 FIN exome

AF:

0.386

Gnomad4 NFE exome

AF:

0.347

Gnomad4 OTH exome

AF:

0.340

GnomAD4 genome

AF:

0.306

AC:

46507

AN:

152040

Hom.:

7599

Cov.:

AF XY:

0.307

AC XY:

22787

AN XY:

74326

show subpopulations

Gnomad4 AFR

AF:

0.202

Gnomad4 AMR

AF:

0.275

Gnomad4 ASJ

AF:

0.407

Gnomad4 EAS

AF:

0.399

Gnomad4 SAS

AF:

0.297

Gnomad4 FIN

AF:

0.405

Gnomad4 NFE

AF:

0.347

Gnomad4 OTH

AF:

0.316

Alfa

AF:

0.323

Hom.:

6590

Bravo

AF:

0.295

Asia WGS

AF:

0.324

AC:

1125

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:6Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

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 48% of patients studied by a panel of primary immunodeficiencies. Number of patients: 46. Only high quality variants are reported. -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Mar 29, 2016	Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

not provided

Benign:1Other:1

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
not provided, no classification provided	phenotyping only	GenomeConnect, ClinGen	-	Variant interpreted as Benign and reported on 04-27-2020 by Lab or GTR ID 500031. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant. This variant was reported in an individual referred for clinical diagnostic genetic testing. -

Pityriasis rubra pilaris

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

Psoriasis 2

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

Pityriasis rubra pilaris;C1864497:Psoriasis 2

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

4.5

DANN

Benign

0.52

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00017

dbscSNV1_RF

Benign

0.036

SpliceAI score (max)

0.13

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