17-80181089-T-TAAAA

Variant names:

• chr17-80181089-T-TAAAA
• rs60307812
• NM_001366385.1:c.-20-319_-20-316dupAAAA

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001366385.1(CARD14):​c.-20-319_-20-316dupAAAA variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.20 (2811 hom., cov: 20)
• Consequence: CARD14 NM_001366385.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.511
• 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: 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 -10 ACMG points.

• BP6: Variant 17-80181089-T-TAAAA is Benign according to our data. Variant chr17-80181089-T-TAAAA is described in ClinVar as Benign. ClinVar VariationId is 1252159.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.232 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.-20-319_-20-316dupAAAA		intron	N/A	NP_001353314.1	Q9BXL6-1
	CARD14	NM_024110.4		c.-20-319_-20-316dupAAAA		intron	N/A	NP_077015.2	Q9BXL6-1
	CARD14	NM_001257970.1		c.-20-319_-20-316dupAAAA		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.-20-330_-20-329insAAAA		intron	N/A	ENSP00000498071.1	Q9BXL6-1
	CARD14	ENST00000344227.6	TSL:1	c.-20-330_-20-329insAAAA		intron	N/A	ENSP00000344549.2	Q9BXL6-1
	CARD14	ENST00000570421.5	TSL:1	c.-20-330_-20-329insAAAA		intron	N/A	ENSP00000461806.1	Q9BXL6-2

Frequencies

GnomAD3 genomes AF: 0.201 AC: 28386 AN: 141004 Hom.: 2807 Cov.: 20

Gnomad AFR AF: 0.228

Gnomad AMI AF: 0.294

Gnomad AMR AF: 0.148

Gnomad ASJ AF: 0.104

Gnomad EAS AF: 0.243

Gnomad SAS AF: 0.128

Gnomad FIN AF: 0.197

Gnomad MID AF: 0.119

Gnomad NFE AF: 0.204

Gnomad OTH AF: 0.166

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.201 AC: 28402 AN: 141046 Hom.: 2811 Cov.: 20 AF XY: 0.197 AC XY: 13449 AN XY: 68106

African (AFR) AF: 0.228 AC: 8814 AN: 38616

American (AMR) AF: 0.148 AC: 2079 AN: 14048

Ashkenazi Jewish (ASJ) AF: 0.104 AC: 347 AN: 3328

East Asian (EAS) AF: 0.243 AC: 1182 AN: 4856

South Asian (SAS) AF: 0.129 AC: 570 AN: 4434

European-Finnish (FIN) AF: 0.197 AC: 1641 AN: 8322

Middle Eastern (MID) AF: 0.122 AC: 34 AN: 278

European-Non Finnish (NFE) AF: 0.204 AC: 13149 AN: 64342

Other (OTH) AF: 0.169 AC: 331 AN: 1954

Alfa AF: 0.0810 Hom.: 106

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.51
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs60307812; hg19: chr17-78154888;