rs28674001

Variant names:

• chr17-80188371-G-A
• rs28674001
• NM_001366385.1:c.676-6G>A

Your query was ambiguous. Multiple possible variants found:

• chr17-80188371-G-A
• chr17-80188371-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.676-6G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.339 in 1,604,012 control chromosomes in the GnomAD database, including 94,043 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.31 (7599 hom., cov: 32)
  • Exomes 𝑓: 0.34 (86444 hom.)
• Consequence: CARD14 NM_001366385.1 splice_region, intron
• Scores: Splicing: ADA: 0.0001668
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6 O:1
• Conservation: PhyloP100: 0.0180
• Publications: 16 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 17-80188371-G-A is Benign according to our data. Variant chr17-80188371-G-A is described in ClinVar as Benign. ClinVar VariationId is 402484.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.385 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.676-6G>A		splice_region intron	N/A	NP_001353314.1
	CARD14	NM_024110.4		c.676-6G>A		splice_region intron	N/A	NP_077015.2
	CARD14	NM_001257970.1		c.676-6G>A		splice_region intron	N/A	NP_001244899.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CARD14	ENST00000648509.2	MANE Select	c.676-6G>A		splice_region intron	N/A	ENSP00000498071.1
	CARD14	ENST00000344227.6	TSL:1	c.676-6G>A		splice_region intron	N/A	ENSP00000344549.2
	CARD14	ENST00000570421.5	TSL:1	c.676-6G>A		splice_region intron	N/A	ENSP00000461806.1

Frequencies

GnomAD3 genomes AF: 0.306 AC: 46494 AN: 151920 Hom.: 7596 Cov.: 32

Gnomad AFR AF: 0.202

Gnomad AMI AF: 0.410

Gnomad AMR AF: 0.275

Gnomad ASJ AF: 0.407

Gnomad EAS AF: 0.399

Gnomad SAS AF: 0.295

Gnomad FIN AF: 0.405

Gnomad MID AF: 0.402

Gnomad NFE AF: 0.347

Gnomad OTH AF: 0.315

GnomAD2 exomes AF: 0.329 AC: 79366 AN: 240926 AF XY: 0.335

Gnomad AFR exome AF: 0.198

Gnomad AMR exome AF: 0.260

Gnomad ASJ exome AF: 0.409

Gnomad EAS exome AF: 0.400

Gnomad FIN exome AF: 0.394

Gnomad NFE exome AF: 0.348

Gnomad OTH exome AF: 0.340

GnomAD4 exome AF: 0.343 AC: 497387 AN: 1451972 Hom.: 86444 Cov.: 33 AF XY: 0.342 AC XY: 247135 AN XY: 722104

African (AFR) AF: 0.200 AC: 6606 AN: 33050

American (AMR) AF: 0.263 AC: 11434 AN: 43428

Ashkenazi Jewish (ASJ) AF: 0.415 AC: 10773 AN: 25962

East Asian (EAS) AF: 0.427 AC: 16508 AN: 38682

South Asian (SAS) AF: 0.287 AC: 24324 AN: 84656

European-Finnish (FIN) AF: 0.386 AC: 20500 AN: 53114

Middle Eastern (MID) AF: 0.376 AC: 2159 AN: 5744

European-Non Finnish (NFE) AF: 0.347 AC: 384665 AN: 1107326

Other (OTH) AF: 0.340 AC: 20418 AN: 60010

GnomAD4 genome AF: 0.306 AC: 46507 AN: 152040 Hom.: 7599 Cov.: 32 AF XY: 0.307 AC XY: 22787 AN XY: 74326

African (AFR) AF: 0.202 AC: 8360 AN: 41454

American (AMR) AF: 0.275 AC: 4199 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.407 AC: 1412 AN: 3466

East Asian (EAS) AF: 0.399 AC: 2062 AN: 5168

South Asian (SAS) AF: 0.297 AC: 1432 AN: 4824

European-Finnish (FIN) AF: 0.405 AC: 4280 AN: 10572

Middle Eastern (MID) AF: 0.395 AC: 116 AN: 294

European-Non Finnish (NFE) AF: 0.347 AC: 23606 AN: 67960

Other (OTH) AF: 0.316 AC: 668 AN: 2112

Alfa AF: 0.329 Hom.: 9094

Bravo AF: 0.295

Asia WGS AF: 0.324 AC: 1125 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	4.5
DANN	Benign	0.52
PhyloP100		0.018
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00017
dbscSNV1_RF	Benign	0.036
SpliceAI score (max)		0.13		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: rs28674001; hg19: chr17-78162170; COSMIC: COSV60122337; COSMIC: COSV60122337;