NM_001366385.1:c.378G>A

Variant names:

• chr17-80183941-G-A
• rs138552007
• NM_001366385.1:c.378G>A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_001366385.1(CARD14):​c.378G>A​(p.Glu126Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00411 in 1,532,298 control chromosomes in the GnomAD database, including 22 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0025 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0043 (22 hom.)
• Consequence: CARD14 NM_001366385.1 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 1.32
• Publications: 1 publications found

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

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BP6: Variant 17-80183941-G-A is Benign according to our data. Variant chr17-80183941-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 458105.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.32 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00246 (375/152306) while in subpopulation NFE AF = 0.0041 (279/68022). AF 95% confidence interval is 0.00371. There are 0 homozygotes in GnomAd4. There are 177 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High AC in GnomAd4 at 375 AD gene.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CARD14	NM_001366385.1	MANE Select	c.378G>A	p.Glu126Glu	synonymous	Exon 7 of 24	NP_001353314.1	Q9BXL6-1
	CARD14	NM_024110.4		c.378G>A	p.Glu126Glu	synonymous	Exon 4 of 21	NP_077015.2	Q9BXL6-1
	CARD14	NM_001257970.1		c.378G>A	p.Glu126Glu	synonymous	Exon 4 of 15	NP_001244899.1	Q9BXL6-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CARD14	ENST00000648509.2	MANE Select	c.378G>A	p.Glu126Glu	synonymous	Exon 7 of 24	ENSP00000498071.1	Q9BXL6-1
	CARD14	ENST00000344227.6	TSL:1	c.378G>A	p.Glu126Glu	synonymous	Exon 4 of 21	ENSP00000344549.2	Q9BXL6-1
	CARD14	ENST00000570421.5	TSL:1	c.378G>A	p.Glu126Glu	synonymous	Exon 4 of 15	ENSP00000461806.1	Q9BXL6-2

Frequencies

GnomAD3 genomes AF: 0.00246 AC: 374 AN: 152188 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00104

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00203

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00166

Gnomad FIN AF: 0.000942

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00410

Gnomad OTH AF: 0.00143

GnomAD2 exomes AF: 0.00217 AC: 375 AN: 172878 AF XY: 0.00249

Gnomad AFR exome AF: 0.000412

Gnomad AMR exome AF: 0.000934

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000443

Gnomad NFE exome AF: 0.00386

Gnomad OTH exome AF: 0.00199

GnomAD4 exome AF: 0.00430 AC: 5929 AN: 1379992 Hom.: 22 Cov.: 30 AF XY: 0.00418 AC XY: 2829 AN XY: 676706

African (AFR) AF: 0.000602 AC: 19 AN: 31568

American (AMR) AF: 0.00113 AC: 39 AN: 34422

Ashkenazi Jewish (ASJ) AF: 0.0000932 AC: 2 AN: 21464

East Asian (EAS) AF: 0.0000261 AC: 1 AN: 38386

South Asian (SAS) AF: 0.00161 AC: 116 AN: 72128

European-Finnish (FIN) AF: 0.000631 AC: 31 AN: 49162

Middle Eastern (MID) AF: 0.000920 AC: 5 AN: 5434

European-Non Finnish (NFE) AF: 0.00511 AC: 5469 AN: 1070390

Other (OTH) AF: 0.00433 AC: 247 AN: 57038

GnomAD4 genome AF: 0.00246 AC: 375 AN: 152306 Hom.: 0 Cov.: 33 AF XY: 0.00238 AC XY: 177 AN XY: 74464

African (AFR) AF: 0.00103 AC: 43 AN: 41564

American (AMR) AF: 0.00203 AC: 31 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5182

South Asian (SAS) AF: 0.00166 AC: 8 AN: 4826

European-Finnish (FIN) AF: 0.000942 AC: 10 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00410 AC: 279 AN: 68022

Other (OTH) AF: 0.00142 AC: 3 AN: 2114

Alfa AF: 0.00272 Hom.: 0

Bravo AF: 0.00245

Asia WGS AF: 0.00173 AC: 6 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Autoinflammatory syndrome (1)
-	-	1	not specified (1)
-	-	1	Pityriasis rubra pilaris;C1864497:Psoriasis 2 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	6.7
DANN	Benign	0.85
PhyloP100		1.3
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs138552007; hg19: chr17-78157740;