rs113127952

Variant names:

• chr17-80198546-G-A
• rs113127952
• NM_001366385.1:c.1806G>A

Your query was ambiguous. Multiple possible variants found:

• chr17-80198546-G-A
• chr17-80198546-G-C
• chr17-80198546-G-T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_001366385.1(CARD14):​c.1806G>A​(p.Ser602Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000413 in 1,613,096 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0018 (2 hom., cov: 32)
  • Exomes 𝑓: 0.00027 (5 hom.)
• Consequence: CARD14 NM_001366385.1 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -6.35
• 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: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 17-80198546-G-A is Benign according to our data. Variant chr17-80198546-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 527879.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-6.35 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00179 (272/152284) while in subpopulation AFR AF = 0.00614 (255/41556). AF 95% confidence interval is 0.00552. There are 2 homozygotes in GnomAd4. There are 133 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 272 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CARD14	NM_001366385.1	MANE Select	c.1806G>A	p.Ser602Ser	synonymous	Exon 16 of 24	NP_001353314.1
	CARD14	NM_024110.4		c.1806G>A	p.Ser602Ser	synonymous	Exon 13 of 21	NP_077015.2
	CARD14	NM_001257970.1		c.1806G>A	p.Ser602Ser	synonymous	Exon 13 of 15	NP_001244899.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CARD14	ENST00000648509.2	MANE Select	c.1806G>A	p.Ser602Ser	synonymous	Exon 16 of 24	ENSP00000498071.1
	CARD14	ENST00000344227.6	TSL:1	c.1806G>A	p.Ser602Ser	synonymous	Exon 13 of 21	ENSP00000344549.2
	CARD14	ENST00000570421.5	TSL:1	c.1806G>A	p.Ser602Ser	synonymous	Exon 13 of 15	ENSP00000461806.1

Frequencies

GnomAD3 genomes AF: 0.00174 AC: 265 AN: 152166 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.00599

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000720

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.000955

GnomAD2 exomes AF: 0.000438 AC: 109 AN: 249092 AF XY: 0.000311

Gnomad AFR exome AF: 0.00547

Gnomad AMR exome AF: 0.000434

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000268

Gnomad OTH exome AF: 0.000164

GnomAD4 exome AF: 0.000270 AC: 395 AN: 1460812 Hom.: 5 Cov.: 32 AF XY: 0.000220 AC XY: 160 AN XY: 726726

African (AFR) AF: 0.00726 AC: 243 AN: 33474

American (AMR) AF: 0.000514 AC: 23 AN: 44706

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26122

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.0000696 AC: 6 AN: 86236

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52608

Middle Eastern (MID) AF: 0.00208 AC: 12 AN: 5768

European-Non Finnish (NFE) AF: 0.0000459 AC: 51 AN: 1111836

Other (OTH) AF: 0.000994 AC: 60 AN: 60368

GnomAD4 genome AF: 0.00179 AC: 272 AN: 152284 Hom.: 2 Cov.: 32 AF XY: 0.00179 AC XY: 133 AN XY: 74466

African (AFR) AF: 0.00614 AC: 255 AN: 41556

American (AMR) AF: 0.000719 AC: 11 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

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

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 68008

Other (OTH) AF: 0.000945 AC: 2 AN: 2116

Alfa AF: 0.000736 Hom.: 0

Bravo AF: 0.00211

Asia WGS AF: 0.000866 AC: 3 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.00

ClinVar

ClinVar submissions as Germline

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.035
DANN	Benign	0.93
PhyloP100		-6.3
Mutation Taster		=97/3	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: rs113127952; hg19: chr17-78172345;