chr17-80189160-T-C

Variant names:

• chr17-80189160-T-C
• rs8065364
• NM_001366385.1:c.844-593T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001366385.1(CARD14):​c.844-593T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.282 in 152,070 control chromosomes in the GnomAD database, including 6,201 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.28 (6201 hom., cov: 32)
• Consequence: CARD14 NM_001366385.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0910
• Publications: 15 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: G2P, Labcorp Genetics (formerly Invitae), Orphanet, Genomics England PanelApp
• psoriasis 2

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae), Genomics England PanelApp

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.298 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CARD14	NM_001366385.1	MANE Select	c.844-593T>C		intron	N/A	NP_001353314.1
	CARD14	NM_024110.4		c.844-593T>C		intron	N/A	NP_077015.2
	CARD14	NM_001257970.1		c.844-593T>C		intron	N/A	NP_001244899.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CARD14	ENST00000648509.2	MANE Select	c.844-593T>C		intron	N/A	ENSP00000498071.1
	CARD14	ENST00000344227.6	TSL:1	c.844-593T>C		intron	N/A	ENSP00000344549.2
	CARD14	ENST00000570421.5	TSL:1	c.844-593T>C		intron	N/A	ENSP00000461806.1

Frequencies

GnomAD3 genomes AF: 0.282 AC: 42858 AN: 151952 Hom.: 6193 Cov.: 32

Gnomad AFR AF: 0.259

Gnomad AMI AF: 0.388

Gnomad AMR AF: 0.218

Gnomad ASJ AF: 0.374

Gnomad EAS AF: 0.285

Gnomad SAS AF: 0.234

Gnomad FIN AF: 0.319

Gnomad MID AF: 0.370

Gnomad NFE AF: 0.301

Gnomad OTH AF: 0.283

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

GnomAD4 genome AF: 0.282 AC: 42895 AN: 152070 Hom.: 6201 Cov.: 32 AF XY: 0.279 AC XY: 20707 AN XY: 74342

African (AFR) AF: 0.259 AC: 10740 AN: 41460

American (AMR) AF: 0.218 AC: 3333 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.374 AC: 1296 AN: 3466

East Asian (EAS) AF: 0.285 AC: 1470 AN: 5158

South Asian (SAS) AF: 0.235 AC: 1136 AN: 4830

European-Finnish (FIN) AF: 0.319 AC: 3379 AN: 10582

Middle Eastern (MID) AF: 0.374 AC: 110 AN: 294

European-Non Finnish (NFE) AF: 0.301 AC: 20473 AN: 67978

Other (OTH) AF: 0.287 AC: 606 AN: 2110

Alfa AF: 0.298 Hom.: 26486

Bravo AF: 0.278

Asia WGS AF: 0.247 AC: 862 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.3
DANN	Benign	0.41
PhyloP100		-0.091
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: rs8065364; hg19: chr17-78162959;