dbSNP rs139274935: CARD14:p.Ser553Ser (chr17-80198399-C-T) – ACMG Classification: Benign (-18 pts)

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_StrongBP6_Very_StrongBP7BS1BS2_Supporting

The NM_001366385.1(CARD14):c.1659C>T(p.Ser553Ser) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000525 in 1,597,498 control chromosomes in the GnomAD database, including 2 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 Likely benign (★★).

Frequency

Genomes: 𝑓 0.00037 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00054 ( 2 hom. )

Consequence

CARD14
NM_001366385.1 splice_region, synonymous

Scores

Splicing: ADA: 0.0009650

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 2.22

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

familial pityriasis rubra pilaris
Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae), G2P, Orphanet
psoriasis 2
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp, G2P

CARD14 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

BP6

Variant 17-80198399-C-T is Benign according to our data. Variant chr17-80198399-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 527881.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=2.22 with no splicing effect.

BS1

Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.000368 (56/152340) while in subpopulation EAS AF = 0.00058 (3/5174). AF 95% confidence interval is 0.000354. There are 0 homozygotes in GnomAd4. There are 33 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High AC in GnomAd4 at 56 AD gene. Variant has AC lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001366385.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CARD14	NM_001366385.1	MANE Select	c.1659C>T	p.Ser553Ser	splice_region synonymous	Exon 16 of 24	NP_001353314.1	Q9BXL6-1
CARD14	NM_024110.4		c.1659C>T	p.Ser553Ser	splice_region synonymous	Exon 13 of 21	NP_077015.2	Q9BXL6-1
CARD14	NM_001257970.1		c.1659C>T	p.Ser553Ser	splice_region synonymous	Exon 13 of 15	NP_001244899.1	Q9BXL6-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CARD14	ENST00000648509.2	MANE Select	c.1659C>T	p.Ser553Ser	splice_region synonymous	Exon 16 of 24	ENSP00000498071.1	Q9BXL6-1
CARD14	ENST00000344227.6	TSL:1	c.1659C>T	p.Ser553Ser	splice_region synonymous	Exon 13 of 21	ENSP00000344549.2	Q9BXL6-1
CARD14	ENST00000570421.5	TSL:1	c.1659C>T	p.Ser553Ser	splice_region synonymous	Exon 13 of 15	ENSP00000461806.1	Q9BXL6-2

Frequencies

GnomAD3 genomes

AF:

0.000368

AC:

AN:

152222

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000965

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000393

Gnomad ASJ

AF:

0.00173

Gnomad EAS

AF:

0.000578

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000485

Gnomad OTH

AF:

0.000956

GnomAD2 exomes

AF:

0.000490

AC:

118

AN:

240834

AF XY:

0.000460

show subpopulations

Gnomad AFR exome

AF:

0.0000638

Gnomad AMR exome

AF:

0.000589

Gnomad ASJ exome

AF:

0.00375

Gnomad EAS exome

AF:

0.000715

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000378

Gnomad OTH exome

AF:

0.000683

GnomAD4 exome

AF:

0.000542

AC:

783

AN:

1445158

Hom.:

Cov.:

AF XY:

0.000533

AC XY:

382

AN XY:

716342

show subpopulations

African (AFR)

AF:

0.0000601

AC:

AN:

33282

American (AMR)

AF:

0.000544

AC:

AN:

44086

Ashkenazi Jewish (ASJ)

AF:

0.00388

AC:

AN:

25238

East Asian (EAS)

AF:

0.000508

AC:

AN:

39384

South Asian (SAS)

AF:

0.000249

AC:

AN:

84460

European-Finnish (FIN)

AF:

0.0000193

AC:

AN:

51762

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5698

European-Non Finnish (NFE)

AF:

0.000534

AC:

588

AN:

1101624

Other (OTH)

AF:

0.000486

AC:

AN:

59624

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

140

187

234

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

112

140

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000368

AC:

AN:

152340

Hom.:

Cov.:

AF XY:

0.000443

AC XY:

AN XY:

74488

show subpopulations

African (AFR)

AF:

0.0000962

AC:

AN:

41584

American (AMR)

AF:

0.000392

AC:

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00173

AC:

AN:

3472

East Asian (EAS)

AF:

0.000580

AC:

AN:

5174

South Asian (SAS)

AF:

0.000414

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000485

AC:

AN:

68034

Other (OTH)

AF:

0.000946

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000592

Hom.:

Bravo

AF:

0.000491

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Autoinflammatory syndrome (1)

not provided (1)

Pityriasis rubra pilaris;C1864497:Psoriasis 2 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

(source)

DANN

Benign

0.82

PhyloP100

2.2

Mutation Taster

=80/20

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00097

dbscSNV1_RF

Benign

0.15

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over