NM_001366385.1:c.-20-36A>C

Variant names:

• chr17-80181383-A-C
• rs9906472
• NM_001366385.1:c.-20-36A>C

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.-20-36A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.542 in 1,495,346 control chromosomes in the GnomAD database, including 224,182 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). There are indicators that this mutation may affect the branch point..

• Frequency:
  • Genomes: 𝑓 0.59 (28239 hom., cov: 32)
  • Exomes 𝑓: 0.54 (195943 hom.)
• Consequence: CARD14 NM_001366385.1 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.239
• Publications: 9 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: This position, referring to a specific DNA site, is a probable branch point but is likely benign (scored 1 / 10, using the threshold of <=3). The score ranges from 0 to 10, with values ≤3 considered benign and >5 classified as pathogenic. Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BP6: Variant 17-80181383-A-C is Benign according to our data. Variant chr17-80181383-A-C is described in ClinVar as Benign. ClinVar VariationId is 1260535.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.773 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.-20-36A>C		intron	N/A	NP_001353314.1	Q9BXL6-1
	CARD14	NM_024110.4		c.-20-36A>C		intron	N/A	NP_077015.2	Q9BXL6-1
	CARD14	NM_001257970.1		c.-20-36A>C		intron	N/A	NP_001244899.1	Q9BXL6-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CARD14	ENST00000648509.2	MANE Select	c.-20-36A>C		intron	N/A	ENSP00000498071.1	Q9BXL6-1
	CARD14	ENST00000344227.6	TSL:1	c.-20-36A>C		intron	N/A	ENSP00000344549.2	Q9BXL6-1
	CARD14	ENST00000570421.5	TSL:1	c.-20-36A>C		intron	N/A	ENSP00000461806.1	Q9BXL6-2

Frequencies

GnomAD3 genomes AF: 0.595 AC: 90379 AN: 151950 Hom.: 28199 Cov.: 32

Gnomad AFR AF: 0.779

Gnomad AMI AF: 0.496

Gnomad AMR AF: 0.424

Gnomad ASJ AF: 0.554

Gnomad EAS AF: 0.652

Gnomad SAS AF: 0.609

Gnomad FIN AF: 0.603

Gnomad MID AF: 0.551

Gnomad NFE AF: 0.519

Gnomad OTH AF: 0.552

GnomAD4 exome AF: 0.536 AC: 719992 AN: 1343278 Hom.: 195943 Cov.: 21 AF XY: 0.537 AC XY: 355163 AN XY: 661014

African (AFR) AF: 0.793 AC: 24211 AN: 30514

American (AMR) AF: 0.363 AC: 12315 AN: 33970

Ashkenazi Jewish (ASJ) AF: 0.557 AC: 13360 AN: 23972

East Asian (EAS) AF: 0.697 AC: 24496 AN: 35162

South Asian (SAS) AF: 0.593 AC: 45558 AN: 76864

European-Finnish (FIN) AF: 0.591 AC: 28378 AN: 48030

Middle Eastern (MID) AF: 0.593 AC: 3146 AN: 5302

European-Non Finnish (NFE) AF: 0.521 AC: 538117 AN: 1033726

Other (OTH) AF: 0.546 AC: 30411 AN: 55738

GnomAD4 genome AF: 0.595 AC: 90471 AN: 152068 Hom.: 28239 Cov.: 32 AF XY: 0.594 AC XY: 44159 AN XY: 74340

African (AFR) AF: 0.780 AC: 32351 AN: 41492

American (AMR) AF: 0.424 AC: 6473 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.554 AC: 1921 AN: 3470

East Asian (EAS) AF: 0.652 AC: 3373 AN: 5174

South Asian (SAS) AF: 0.610 AC: 2945 AN: 4828

European-Finnish (FIN) AF: 0.603 AC: 6382 AN: 10576

Middle Eastern (MID) AF: 0.541 AC: 159 AN: 294

European-Non Finnish (NFE) AF: 0.519 AC: 35253 AN: 67942

Other (OTH) AF: 0.553 AC: 1163 AN: 2102

Alfa AF: 0.431 Hom.: 1215

Bravo AF: 0.589

Asia WGS AF: 0.621 AC: 2159 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.0
DANN	Benign	0.47
PhyloP100		-0.24
BranchPoint Hunter		1.0
Mutation Taster		=100/0	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: rs9906472; hg19: chr17-78155182; COSMIC: COSV107424600; COSMIC: COSV107424600;