rs34367357

Variant names:

• chr17-80198493-G-A
• rs34367357
• NM_001366385.1:c.1753G>A

Your query was ambiguous. Multiple possible variants found:

• chr17-80198493-G-A
• chr17-80198493-G-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001366385.1(CARD14):​c.1753G>A​(p.Val585Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0794 in 1,613,510 control chromosomes in the GnomAD database, including 5,603 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 Benign,association (★★). Synonymous variant affecting the same amino acid position (i.e. V585V) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.067 (403 hom., cov: 32)
  • Exomes 𝑓: 0.081 (5200 hom.)
• Consequence: CARD14 NM_001366385.1 missense
• Clinical Significance: Benign; association criteria provided, multiple submitters, no conflicts B:4 O:1
• Conservation: PhyloP100: -0.173
• Publications: 23 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=0.001291275).
• BP6: Variant 17-80198493-G-A is Benign according to our data. Variant chr17-80198493-G-A is described in ClinVar as Benign|association. ClinVar VariationId is 1167399.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.113 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.1753G>A	p.Val585Ile	missense	Exon 16 of 24	NP_001353314.1	Q9BXL6-1
	CARD14	NM_024110.4		c.1753G>A	p.Val585Ile	missense	Exon 13 of 21	NP_077015.2	Q9BXL6-1
	CARD14	NM_001257970.1		c.1753G>A	p.Val585Ile	missense	Exon 13 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.1753G>A	p.Val585Ile	missense	Exon 16 of 24	ENSP00000498071.1	Q9BXL6-1
	CARD14	ENST00000344227.6	TSL:1	c.1753G>A	p.Val585Ile	missense	Exon 13 of 21	ENSP00000344549.2	Q9BXL6-1
	CARD14	ENST00000570421.5	TSL:1	c.1753G>A	p.Val585Ile	missense	Exon 13 of 15	ENSP00000461806.1	Q9BXL6-2

Frequencies

GnomAD3 genomes AF: 0.0672 AC: 10222 AN: 152220 Hom.: 407 Cov.: 32

Gnomad AFR AF: 0.0304

Gnomad AMI AF: 0.0800

Gnomad AMR AF: 0.118

Gnomad ASJ AF: 0.0401

Gnomad EAS AF: 0.0823

Gnomad SAS AF: 0.0874

Gnomad FIN AF: 0.0607

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0778

Gnomad OTH AF: 0.0670

GnomAD2 exomes AF: 0.0872 AC: 21892 AN: 250978 AF XY: 0.0852

Gnomad AFR exome AF: 0.0300

Gnomad AMR exome AF: 0.182

Gnomad ASJ exome AF: 0.0398

Gnomad EAS exome AF: 0.0822

Gnomad FIN exome AF: 0.0632

Gnomad NFE exome AF: 0.0771

Gnomad OTH exome AF: 0.0767

GnomAD4 exome AF: 0.0807 AC: 117862 AN: 1461172 Hom.: 5200 Cov.: 32 AF XY: 0.0802 AC XY: 58326 AN XY: 726914

African (AFR) AF: 0.0275 AC: 921 AN: 33476

American (AMR) AF: 0.174 AC: 7765 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.0399 AC: 1042 AN: 26122

East Asian (EAS) AF: 0.0860 AC: 3415 AN: 39694

South Asian (SAS) AF: 0.0846 AC: 7295 AN: 86248

European-Finnish (FIN) AF: 0.0635 AC: 3362 AN: 52924

Middle Eastern (MID) AF: 0.0610 AC: 352 AN: 5768

European-Non Finnish (NFE) AF: 0.0800 AC: 88989 AN: 1111852

Other (OTH) AF: 0.0782 AC: 4721 AN: 60376

GnomAD4 genome AF: 0.0671 AC: 10222 AN: 152338 Hom.: 403 Cov.: 32 AF XY: 0.0686 AC XY: 5112 AN XY: 74490

African (AFR) AF: 0.0305 AC: 1270 AN: 41582

American (AMR) AF: 0.117 AC: 1798 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0401 AC: 139 AN: 3468

East Asian (EAS) AF: 0.0823 AC: 427 AN: 5186

South Asian (SAS) AF: 0.0873 AC: 421 AN: 4824

European-Finnish (FIN) AF: 0.0607 AC: 645 AN: 10632

Middle Eastern (MID) AF: 0.0646 AC: 19 AN: 294

European-Non Finnish (NFE) AF: 0.0778 AC: 5290 AN: 68022

Other (OTH) AF: 0.0663 AC: 140 AN: 2112

Alfa AF: 0.0735 Hom.: 1004

Bravo AF: 0.0689

TwinsUK AF: 0.0707 AC: 262

ALSPAC AF: 0.0810 AC: 312

ESP6500AA AF: 0.0315 AC: 139

ESP6500EA AF: 0.0691 AC: 594

ExAC AF: 0.0835 AC: 10134

Asia WGS AF: 0.0840 AC: 290 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign; association

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	not specified (1)
-	-	1	Pityriasis rubra pilaris;C1864497:Psoriasis 2 (1)
-	-	-	Pityriasis rubra pilaris (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.081
BayesDel_addAF	Benign	-0.66	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	0.31
DANN	Benign	0.84
DEOGEN2	Benign	0.0062	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.066	N
LIST_S2	Benign	0.58	T
MetaRNN	Benign	0.0013	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	-0.21	N
PhyloP100		-0.17
PrimateAI	Benign	0.32	T
PROVEAN	Benign	0.25	N
REVEL	Benign	0.022
Sift	Benign	0.85	T
Sift4G	Benign	1.0	T
Polyphen		0.0060	B
Vest4		0.079
MPC		0.12
ClinPred		0.0011	T
GERP RS		-1.4
Varity_R		0.018
gMVP		0.088
Mutation Taster		=99/1	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: rs34367357; hg19: chr17-78172292; COSMIC: COSV60124390; COSMIC: COSV60124390;