rs62074378

Variant summary

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

The NM_001366385.1(CARD14):​c.1371G>A​(p.Ser457Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0416 in 1,608,020 control chromosomes in the GnomAD database, including 1,584 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.031 ( 101 hom., cov: 32)
Exomes 𝑓: 0.043 ( 1483 hom. )

Consequence

CARD14
NM_001366385.1 synonymous

Scores

2

Clinical Significance

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

Conservation

PhyloP100: -2.07
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.91).
BP6
Variant 17-80195205-G-A is Benign according to our data. Variant chr17-80195205-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 458086.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-2.07 with no splicing effect.
BS1
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0312 (4752/152242) while in subpopulation NFE AF= 0.0462 (3141/67990). AF 95% confidence interval is 0.0448. There are 101 homozygotes in gnomad4. There are 2276 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High AC in GnomAd4 at 4752 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
CARD14NM_001366385.1 linkuse as main transcriptc.1371G>A p.Ser457Ser synonymous_variant 13/24 ENST00000648509.2 NP_001353314.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
CARD14ENST00000648509.2 linkuse as main transcriptc.1371G>A p.Ser457Ser synonymous_variant 13/24 NM_001366385.1 ENSP00000498071.1 Q9BXL6-1

Frequencies

GnomAD3 genomes
AF:
0.0313
AC:
4755
AN:
152124
Hom.:
102
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00922
Gnomad AMI
AF:
0.0143
Gnomad AMR
AF:
0.0300
Gnomad ASJ
AF:
0.0291
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.0343
Gnomad FIN
AF:
0.0390
Gnomad MID
AF:
0.0316
Gnomad NFE
AF:
0.0462
Gnomad OTH
AF:
0.0335
GnomAD3 exomes
AF:
0.0339
AC:
8355
AN:
246688
Hom.:
165
AF XY:
0.0350
AC XY:
4681
AN XY:
133760
show subpopulations
Gnomad AFR exome
AF:
0.00947
Gnomad AMR exome
AF:
0.0181
Gnomad ASJ exome
AF:
0.0365
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0324
Gnomad FIN exome
AF:
0.0373
Gnomad NFE exome
AF:
0.0474
Gnomad OTH exome
AF:
0.0361
GnomAD4 exome
AF:
0.0427
AC:
62161
AN:
1455778
Hom.:
1483
Cov.:
31
AF XY:
0.0425
AC XY:
30760
AN XY:
723478
show subpopulations
Gnomad4 AFR exome
AF:
0.00901
Gnomad4 AMR exome
AF:
0.0191
Gnomad4 ASJ exome
AF:
0.0346
Gnomad4 EAS exome
AF:
0.000126
Gnomad4 SAS exome
AF:
0.0335
Gnomad4 FIN exome
AF:
0.0376
Gnomad4 NFE exome
AF:
0.0476
Gnomad4 OTH exome
AF:
0.0374
GnomAD4 genome
AF:
0.0312
AC:
4752
AN:
152242
Hom.:
101
Cov.:
32
AF XY:
0.0306
AC XY:
2276
AN XY:
74442
show subpopulations
Gnomad4 AFR
AF:
0.00920
Gnomad4 AMR
AF:
0.0300
Gnomad4 ASJ
AF:
0.0291
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.0337
Gnomad4 FIN
AF:
0.0390
Gnomad4 NFE
AF:
0.0462
Gnomad4 OTH
AF:
0.0331
Alfa
AF:
0.0279
Hom.:
31
Bravo
AF:
0.0294
Asia WGS
AF:
0.0150
AC:
54
AN:
3478
EpiCase
AF:
0.0458
EpiControl
AF:
0.0491

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 submitterclinical testingGeneDxJul 09, 2018- -
Likely benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
Pityriasis rubra pilaris;C1864497:Psoriasis 2 Benign:1
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpFeb 01, 2024- -
Autoinflammatory syndrome Benign:1
Benign, criteria provided, single submitterclinical testingGenome Diagnostics Laboratory, The Hospital for Sick ChildrenJan 22, 2022- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.91
CADD
Benign
1.1
DANN
Benign
0.41

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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.

Other links and lift over

dbSNP: rs62074378; hg19: chr17-78169004; API