chr17-80191403-C-T

Variant names:

• chr17-80191403-C-T
• rs74951924
• NM_001366385.1:c.1170C>T

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.1170C>T​(p.Phe390Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0424 in 1,613,730 control chromosomes in the GnomAD database, including 1,633 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.035 (119 hom., cov: 33)
  • Exomes 𝑓: 0.043 (1514 hom.)
• Consequence: CARD14 NM_001366385.1 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -3.15
• Publications: 5 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=-0.47).
• BP6: Variant 17-80191403-C-T is Benign according to our data. Variant chr17-80191403-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 458084.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-3.15 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0355 (5404/152270) while in subpopulation NFE AF = 0.0462 (3144/68004). AF 95% confidence interval is 0.0449. There are 119 homozygotes in GnomAd4. There are 2582 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High AC in GnomAd4 at 5404 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.1170C>T	p.Phe390Phe	synonymous	Exon 11 of 24	NP_001353314.1	Q9BXL6-1
	CARD14	NM_024110.4		c.1170C>T	p.Phe390Phe	synonymous	Exon 8 of 21	NP_077015.2	Q9BXL6-1
	CARD14	NM_001257970.1		c.1170C>T	p.Phe390Phe	synonymous	Exon 8 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.1170C>T	p.Phe390Phe	synonymous	Exon 11 of 24	ENSP00000498071.1	Q9BXL6-1
	CARD14	ENST00000344227.6	TSL:1	c.1170C>T	p.Phe390Phe	synonymous	Exon 8 of 21	ENSP00000344549.2	Q9BXL6-1
	CARD14	ENST00000570421.5	TSL:1	c.1170C>T	p.Phe390Phe	synonymous	Exon 8 of 15	ENSP00000461806.1	Q9BXL6-2

Frequencies

GnomAD3 genomes AF: 0.0355 AC: 5397 AN: 152152 Hom.: 120 Cov.: 33

Gnomad AFR AF: 0.0243

Gnomad AMI AF: 0.0143

Gnomad AMR AF: 0.0308

Gnomad ASJ AF: 0.0291

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0344

Gnomad FIN AF: 0.0391

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0462

Gnomad OTH AF: 0.0339

GnomAD2 exomes AF: 0.0350 AC: 8785 AN: 250654 AF XY: 0.0356

Gnomad AFR exome AF: 0.0245

Gnomad AMR exome AF: 0.0187

Gnomad ASJ exome AF: 0.0367

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0375

Gnomad NFE exome AF: 0.0473

Gnomad OTH exome AF: 0.0362

GnomAD4 exome AF: 0.0431 AC: 63035 AN: 1461460 Hom.: 1514 Cov.: 32 AF XY: 0.0428 AC XY: 31127 AN XY: 727048

African (AFR) AF: 0.0256 AC: 856 AN: 33478

American (AMR) AF: 0.0201 AC: 898 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.0346 AC: 903 AN: 26134

East Asian (EAS) AF: 0.000126 AC: 5 AN: 39698

South Asian (SAS) AF: 0.0338 AC: 2912 AN: 86238

European-Finnish (FIN) AF: 0.0382 AC: 2030 AN: 53086

Middle Eastern (MID) AF: 0.0409 AC: 236 AN: 5768

European-Non Finnish (NFE) AF: 0.0475 AC: 52864 AN: 1111958

Other (OTH) AF: 0.0386 AC: 2331 AN: 60382

GnomAD4 genome AF: 0.0355 AC: 5404 AN: 152270 Hom.: 119 Cov.: 33 AF XY: 0.0347 AC XY: 2582 AN XY: 74450

African (AFR) AF: 0.0245 AC: 1017 AN: 41560

American (AMR) AF: 0.0308 AC: 471 AN: 15312

Ashkenazi Jewish (ASJ) AF: 0.0291 AC: 101 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5156

South Asian (SAS) AF: 0.0338 AC: 163 AN: 4824

European-Finnish (FIN) AF: 0.0391 AC: 415 AN: 10624

Middle Eastern (MID) AF: 0.0306 AC: 9 AN: 294

European-Non Finnish (NFE) AF: 0.0462 AC: 3144 AN: 68004

Other (OTH) AF: 0.0336 AC: 71 AN: 2114

Alfa AF: 0.0400 Hom.: 55

Bravo AF: 0.0344

Asia WGS AF: 0.0170 AC: 60 AN: 3478

EpiCase AF: 0.0452

EpiControl AF: 0.0495

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	Pityriasis rubra pilaris;C1864497:Psoriasis 2 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
CADD	Benign	0.84
DANN	Benign	0.93
PhyloP100		-3.1
Mutation Taster		=100/0	polymorphism (auto)

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: rs74951924; hg19: chr17-78165202;