rs770212092

Variant names:

• chr17-80190856-C-A
• rs770212092
• NM_001366385.1:c.1046C>A

Your query was ambiguous. Multiple possible variants found:

• chr17-80190856-C-A
• chr17-80190856-C-G
• chr17-80190856-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001366385.1(CARD14):​c.1046C>A​(p.Ala349Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,782 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A349V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CARD14 NM_001366385.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.44
• 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: 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.24411237).

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.1046C>A	p.Ala349Glu	missense	Exon 10 of 24	NP_001353314.1
	CARD14	NM_024110.4		c.1046C>A	p.Ala349Glu	missense	Exon 7 of 21	NP_077015.2
	CARD14	NM_001257970.1		c.1046C>A	p.Ala349Glu	missense	Exon 7 of 15	NP_001244899.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CARD14	ENST00000648509.2	MANE Select	c.1046C>A	p.Ala349Glu	missense	Exon 10 of 24	ENSP00000498071.1
	CARD14	ENST00000344227.6	TSL:1	c.1046C>A	p.Ala349Glu	missense	Exon 7 of 21	ENSP00000344549.2
	CARD14	ENST00000570421.5	TSL:1	c.1046C>A	p.Ala349Glu	missense	Exon 7 of 15	ENSP00000461806.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461782 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727196

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53332

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111998

Other (OTH) AF: 0.00 AC: 0 AN: 60392

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Pityriasis rubra pilaris;C1864497:Psoriasis 2 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.26
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	13
DANN	Uncertain	0.99
DEOGEN2	Benign	0.083	T
Eigen	Benign	-0.22
Eigen_PC	Benign	-0.43
FATHMM_MKL	Benign	0.30	N
LIST_S2	Benign	0.69	T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.24	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		1.4
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.12
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.013	D
Polyphen		0.83	P
Vest4		0.39
MutPred		0.41		Loss of MoRF binding (P = 0.0432)
MVP		0.80
MPC		0.54
ClinPred		0.87	D
GERP RS		2.2
Varity_R		0.12
gMVP		0.36
Mutation Taster		=92/8	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: rs770212092; hg19: chr17-78164655;