rs2289539

Positions:

• chr17-80178320-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001366385.1(CARD14):​c.-366-188T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.638 in 152,012 control chromosomes in the GnomAD database, including 31,233 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.64 (31233 hom., cov: 32)
• Consequence: CARD14 NM_001366385.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.786

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.679 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CARD14	NM_001366385.1	c.-366-188T>C		intron_variant		ENST00000648509.2	NP_001353314.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CARD14	ENST00000648509.2	c.-366-188T>C		intron_variant			NM_001366385.1	ENSP00000498071	P1

Frequencies

GnomAD3 genomes AF: 0.638 AC: 96981 AN: 151894 Hom.: 31206 Cov.: 32

Gnomad AFR AF: 0.608

Gnomad AMI AF: 0.578

Gnomad AMR AF: 0.527

Gnomad ASJ AF: 0.735

Gnomad EAS AF: 0.597

Gnomad SAS AF: 0.700

Gnomad FIN AF: 0.684

Gnomad MID AF: 0.737

Gnomad NFE AF: 0.670

Gnomad OTH AF: 0.626

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

GnomAD4 genome AF: 0.638 AC: 97054 AN: 152012 Hom.: 31233 Cov.: 32 AF XY: 0.636 AC XY: 47257 AN XY: 74310

Gnomad4 AFR AF: 0.608

Gnomad4 AMR AF: 0.526

Gnomad4 ASJ AF: 0.735

Gnomad4 EAS AF: 0.596

Gnomad4 SAS AF: 0.699

Gnomad4 FIN AF: 0.684

Gnomad4 NFE AF: 0.670

Gnomad4 OTH AF: 0.627

Alfa AF: 0.667 Hom.: 68563

Bravo AF: 0.626

Asia WGS AF: 0.642 AC: 2236 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.10
DANN	Benign	0.33

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs2289539; hg19: chr17-78152119;