chr17-80206788-A-G

Position:

• chr17-80206788-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001366385.1(CARD14):​c.2692-182A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.543 in 412,262 control chromosomes in the GnomAD database, including 63,297 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.48 (18704 hom., cov: 32)
  • Exomes 𝑓: 0.58 (44593 hom.)
• Consequence: CARD14 NM_001366385.1 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.236

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]

SGSH (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BP6: Variant 17-80206788-A-G is Benign according to our data. Variant chr17-80206788-A-G is described in ClinVar as [Benign]. Clinvar id is 1255138.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.579 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CARD14	NM_001366385.1	c.2692-182A>G		intron_variant		ENST00000648509.2	NP_001353314.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CARD14	ENST00000648509.2	c.2692-182A>G		intron_variant			NM_001366385.1	ENSP00000498071.1

Frequencies

GnomAD3 genomes AF: 0.479 AC: 72742 AN: 151850 Hom.: 18713 Cov.: 32

Gnomad AFR AF: 0.282

Gnomad AMI AF: 0.660

Gnomad AMR AF: 0.436

Gnomad ASJ AF: 0.548

Gnomad EAS AF: 0.573

Gnomad SAS AF: 0.495

Gnomad FIN AF: 0.547

Gnomad MID AF: 0.490

Gnomad NFE AF: 0.584

Gnomad OTH AF: 0.481

GnomAD4 exome AF: 0.581 AC: 151252 AN: 260294 Hom.: 44593 Cov.: 3 AF XY: 0.582 AC XY: 78261 AN XY: 134408

Gnomad4 AFR exome AF: 0.298

Gnomad4 AMR exome AF: 0.435

Gnomad4 ASJ exome AF: 0.553

Gnomad4 EAS exome AF: 0.684

Gnomad4 SAS exome AF: 0.572

Gnomad4 FIN exome AF: 0.562

Gnomad4 NFE exome AF: 0.595

Gnomad4 OTH exome AF: 0.543

GnomAD4 genome AF: 0.479 AC: 72742 AN: 151968 Hom.: 18704 Cov.: 32 AF XY: 0.479 AC XY: 35572 AN XY: 74264

Gnomad4 AFR AF: 0.282

Gnomad4 AMR AF: 0.436

Gnomad4 ASJ AF: 0.548

Gnomad4 EAS AF: 0.573

Gnomad4 SAS AF: 0.495

Gnomad4 FIN AF: 0.547

Gnomad4 NFE AF: 0.584

Gnomad4 OTH AF: 0.480

Alfa AF: 0.421 Hom.: 1400

Bravo AF: 0.458

Asia WGS AF: 0.517 AC: 1796 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 05, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.33
DANN	Benign	0.10

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

LitVar

Other links and lift over

dbSNP: rs4889837; hg19: chr17-78180587;