rs2289539

Variant names:

• chr17-80178320-T-C
• rs2289539
• NM_001366385.1:c.-366-188T>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.-366-188T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.638 in 152,012 control chromosomes in the GnomAD database, including 31,233 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 0.64 (31233 hom., cov: 32)
• Consequence: CARD14 NM_001366385.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.786
• Publications: 13 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.679 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CARD14	NM_001366385.1	MANE Select	c.-366-188T>C		intron	N/A	NP_001353314.1	Q9BXL6-1
	CARD14	NR_047566.2		n.28-188T>C		intron	N/A
	CARD14	NM_024110.4		c.-356T>C		upstream_gene	N/A	NP_077015.2	Q9BXL6-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CARD14	ENST00000648509.2	MANE Select	c.-366-188T>C		intron	N/A	ENSP00000498071.1	Q9BXL6-1
	CARD14	ENST00000651672.1		c.-366-188T>C		intron	N/A	ENSP00000499145.1	A0A494C1N2
	CARD14	ENST00000571427.2	TSL:5	c.-150-206T>C		intron	N/A	ENSP00000516501.1	Q9BXL6-1

Frequencies

GnomAD3 genomes AF: 0.638 AC: 96981 AN: 151894 Hom.: 31206 Cov.: 32

Gnomad AFR AF: 0.608

Gnomad AMI AF: 0.578

Gnomad AMR AF: 0.527

Gnomad ASJ AF: 0.735

Gnomad EAS AF: 0.597

Gnomad SAS AF: 0.700

Gnomad FIN AF: 0.684

Gnomad MID AF: 0.737

Gnomad NFE AF: 0.670

Gnomad OTH AF: 0.626

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

GnomAD4 genome AF: 0.638 AC: 97054 AN: 152012 Hom.: 31233 Cov.: 32 AF XY: 0.636 AC XY: 47257 AN XY: 74310

African (AFR) AF: 0.608 AC: 25188 AN: 41426

American (AMR) AF: 0.526 AC: 8038 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.735 AC: 2553 AN: 3472

East Asian (EAS) AF: 0.596 AC: 3087 AN: 5176

South Asian (SAS) AF: 0.699 AC: 3369 AN: 4820

European-Finnish (FIN) AF: 0.684 AC: 7228 AN: 10570

Middle Eastern (MID) AF: 0.738 AC: 217 AN: 294

European-Non Finnish (NFE) AF: 0.670 AC: 45522 AN: 67960

Other (OTH) AF: 0.627 AC: 1326 AN: 2116

Alfa AF: 0.662 Hom.: 140675

Bravo AF: 0.626

Asia WGS AF: 0.642 AC: 2236 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.10
DANN	Benign	0.33
PhyloP100		-0.79
PromoterAI		0.052	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2289539; hg19: chr17-78152119;