17-80181089-TAAAA-TAAAAAAAAAAAA

Variant names:

• chr17-80181089-T-TAAAAAAAA
• rs60307812
• NM_001366385.1:c.-20-323_-20-316dupAAAAAAAA

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001366385.1(CARD14):​c.-20-323_-20-316dupAAAAAAAA variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.0000071 (0 hom., cov: 20)
• Consequence: CARD14 NM_001366385.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.511
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

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.-20-323_-20-316dupAAAAAAAA		intron	N/A	NP_001353314.1	Q9BXL6-1
	CARD14	NM_024110.4		c.-20-323_-20-316dupAAAAAAAA		intron	N/A	NP_077015.2	Q9BXL6-1
	CARD14	NM_001257970.1		c.-20-323_-20-316dupAAAAAAAA		intron	N/A	NP_001244899.1	Q9BXL6-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CARD14	ENST00000648509.2	MANE Select	c.-20-330_-20-329insAAAAAAAA		intron	N/A	ENSP00000498071.1	Q9BXL6-1
	CARD14	ENST00000344227.6	TSL:1	c.-20-330_-20-329insAAAAAAAA		intron	N/A	ENSP00000344549.2	Q9BXL6-1
	CARD14	ENST00000570421.5	TSL:1	c.-20-330_-20-329insAAAAAAAA		intron	N/A	ENSP00000461806.1	Q9BXL6-2

Frequencies

GnomAD3 genomes AF: 0.00000707 AC: 1 AN: 141448 Hom.: 0 Cov.: 20

Gnomad AFR AF: 0.0000258

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.00000707 AC: 1 AN: 141448 Hom.: 0 Cov.: 20 AF XY: 0.0000146 AC XY: 1 AN XY: 68276

African (AFR) AF: 0.0000258 AC: 1 AN: 38694

American (AMR) AF: 0.00 AC: 0 AN: 14080

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3330

East Asian (EAS) AF: 0.00 AC: 0 AN: 4880

South Asian (SAS) AF: 0.00 AC: 0 AN: 4454

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8398

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 302

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 64498

Other (OTH) AF: 0.00 AC: 0 AN: 1944

Alfa AF: 0.00 Hom.: 106

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.51

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs60307812; hg19: chr17-78154888;