rs56282439

Variant names:

• chr17-80181205-G-A
• rs56282439
• NM_001366385.1:c.-20-214G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001366385.1(CARD14):​c.-20-214G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.09 in 152,130 control chromosomes in the GnomAD database, including 639 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.090 (639 hom., cov: 32)
• Consequence: CARD14 NM_001366385.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.282

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]

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BP6: Variant 17-80181205-G-A is Benign according to our data. Variant chr17-80181205-G-A is described in ClinVar as [Benign]. Clinvar id is 1249345.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.1 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CARD14	NM_001366385.1	c.-20-214G>A		intron_variant	Intron 4 of 23	ENST00000648509.2	NP_001353314.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CARD14	ENST00000648509.2	c.-20-214G>A		intron_variant	Intron 4 of 23		NM_001366385.1	ENSP00000498071.1

Frequencies

GnomAD3 genomes AF: 0.0901 AC: 13689 AN: 152012 Hom.: 640 Cov.: 32

Gnomad AFR AF: 0.103

Gnomad AMI AF: 0.0329

Gnomad AMR AF: 0.0745

Gnomad ASJ AF: 0.155

Gnomad EAS AF: 0.0239

Gnomad SAS AF: 0.0966

Gnomad FIN AF: 0.100

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.0861

Gnomad OTH AF: 0.0883

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

GnomAD4 genome AF: 0.0900 AC: 13694 AN: 152130 Hom.: 639 Cov.: 32 AF XY: 0.0895 AC XY: 6660 AN XY: 74376

African (AFR) AF: 0.103 AC: 4272 AN: 41492

American (AMR) AF: 0.0744 AC: 1137 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.155 AC: 537 AN: 3466

East Asian (EAS) AF: 0.0241 AC: 125 AN: 5178

South Asian (SAS) AF: 0.0958 AC: 462 AN: 4822

European-Finnish (FIN) AF: 0.100 AC: 1062 AN: 10580

Middle Eastern (MID) AF: 0.102 AC: 30 AN: 294

European-Non Finnish (NFE) AF: 0.0861 AC: 5852 AN: 67998

Other (OTH) AF: 0.0888 AC: 187 AN: 2106

Alfa AF: 0.0824 Hom.: 169

Bravo AF: 0.0881

Asia WGS AF: 0.0700 AC: 248 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jul 09, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.4
DANN	Benign	0.54
PhyloP100		-0.28
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

Publications

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Other links and lift over

dbSNP: rs56282439; hg19: chr17-78155004;