Genetic Variant NM_001366385.1:c.-20-36A>T (chr17-80181383-A-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001366385.1(CARD14):c.-20-36A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. There are indicators that this mutation may affect the branch point..

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

CARD14
NM_001366385.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.239

Publications

9 publications found

Variant links:

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

CARD14 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

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=-1.02).

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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CARD14	NM_001366385.1	MANE Select	c.-20-36A>T	intron	N/A	NP_001353314.1	Q9BXL6-1
CARD14	NM_024110.4		c.-20-36A>T	intron	N/A	NP_077015.2	Q9BXL6-1
CARD14	NM_001257970.1		c.-20-36A>T	intron	N/A	NP_001244899.1	Q9BXL6-2

Ensembl Transcripts

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

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1345116

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

661916

African (AFR)

AF:

0.00

AC:

AN:

30542

American (AMR)

AF:

0.00

AC:

AN:

34022

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23990

East Asian (EAS)

AF:

0.00

AC:

AN:

35182

South Asian (SAS)

AF:

0.00

AC:

AN:

76940

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48060

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5308

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1035266

Other (OTH)

AF:

0.00

AC:

AN:

55806

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.87

(source)

DANN

Benign

0.58

PhyloP100

-0.24

BranchPoint Hunter

1.0

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over