rs115582620

Variant names:

• chr17-80181623-G-A
• rs115582620
• NM_001366385.1:c.185G>A

Your query was ambiguous. Multiple possible variants found:

• chr17-80181623-G-A
• chr17-80181623-G-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001366385.1(CARD14):​c.185G>A​(p.Arg62Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00118 in 1,552,610 control chromosomes in the GnomAD database, including 16 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R62W) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0042 (4 hom., cov: 33)
  • Exomes 𝑓: 0.00085 (12 hom.)
• Consequence: CARD14 NM_001366385.1 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4 O:1
• Conservation: PhyloP100: 1.32
• 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0036271214).
• BP6: Variant 17-80181623-G-A is Benign according to our data. Variant chr17-80181623-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 68777.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00423 (644/152316) while in subpopulation AFR AF = 0.0143 (596/41564). AF 95% confidence interval is 0.0134. There are 4 homozygotes in GnomAd4. There are 301 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High AC in GnomAd4 at 644 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.185G>A	p.Arg62Gln	missense	Exon 5 of 24	NP_001353314.1	Q9BXL6-1
	CARD14	NM_024110.4		c.185G>A	p.Arg62Gln	missense	Exon 2 of 21	NP_077015.2	Q9BXL6-1
	CARD14	NM_001257970.1		c.185G>A	p.Arg62Gln	missense	Exon 2 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.185G>A	p.Arg62Gln	missense	Exon 5 of 24	ENSP00000498071.1	Q9BXL6-1
	CARD14	ENST00000344227.6	TSL:1	c.185G>A	p.Arg62Gln	missense	Exon 2 of 21	ENSP00000344549.2	Q9BXL6-1
	CARD14	ENST00000570421.5	TSL:1	c.185G>A	p.Arg62Gln	missense	Exon 2 of 15	ENSP00000461806.1	Q9BXL6-2

Frequencies

GnomAD3 genomes AF: 0.00417 AC: 635 AN: 152198 Hom.: 3 Cov.: 33

Gnomad AFR AF: 0.0142

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00423

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00192

GnomAD2 exomes AF: 0.00138 AC: 212 AN: 153392 AF XY: 0.00101

Gnomad AFR exome AF: 0.0155

Gnomad AMR exome AF: 0.00145

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00326

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000516

Gnomad OTH exome AF: 0.000228

GnomAD4 exome AF: 0.000851 AC: 1191 AN: 1400294 Hom.: 12 Cov.: 32 AF XY: 0.000763 AC XY: 527 AN XY: 691092

African (AFR) AF: 0.0155 AC: 492 AN: 31704

American (AMR) AF: 0.00133 AC: 48 AN: 36054

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25180

East Asian (EAS) AF: 0.0150 AC: 538 AN: 35890

South Asian (SAS) AF: 0.000126 AC: 10 AN: 79336

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48054

Middle Eastern (MID) AF: 0.000182 AC: 1 AN: 5508

European-Non Finnish (NFE) AF: 0.0000315 AC: 34 AN: 1080502

Other (OTH) AF: 0.00117 AC: 68 AN: 58066

GnomAD4 genome AF: 0.00423 AC: 644 AN: 152316 Hom.: 4 Cov.: 33 AF XY: 0.00404 AC XY: 301 AN XY: 74488

African (AFR) AF: 0.0143 AC: 596 AN: 41564

American (AMR) AF: 0.00131 AC: 20 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00424 AC: 22 AN: 5184

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68026

Other (OTH) AF: 0.00190 AC: 4 AN: 2108

Alfa AF: 0.00134 Hom.: 2

Bravo AF: 0.00491

ESP6500AA AF: 0.0128 AC: 55

ESP6500EA AF: 0.000119 AC: 1

ExAC AF: 0.000991 AC: 105

Asia WGS AF: 0.00289 AC: 10 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Autoinflammatory syndrome (1)
-	-	1	CARD14-related disorder (1)
-	-	1	not provided (2)
-	-	1	Pityriasis rubra pilaris;C1864497:Psoriasis 2 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.079
BayesDel_addAF	Benign	-0.58	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	11
DANN	Benign	0.91
DEOGEN2	Benign	0.0066	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.26	N
LIST_S2	Benign	0.59	T
MetaRNN	Benign	0.0036	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.84	L
PhyloP100		1.3
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-0.73	N
REVEL	Benign	0.053
Sift	Benign	0.36	T
Sift4G	Benign	0.46	T
Polyphen		0.0010	B
Vest4		0.13
MVP		0.39
MPC		0.18
ClinPred		0.0063	T
GERP RS		-2.7
Varity_R		0.025
gMVP		0.57
Mutation Taster		=96/4	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: rs115582620; hg19: chr17-78155422; COSMIC: COSV100712589; COSMIC: COSV100712589;