17-80206819-A-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001366385.1(CARD14):c.2692-151A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.54 in 447,944 control chromosomes in the GnomAD database, including 67,540 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.49 (19060 hom., cov: 33)
  • Exomes 𝑓: 0.57 (48480 hom.)
• Consequence: CARD14 NM_001366385.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.03

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:10818): (N-sulfoglucosamine sulfohydrolase) This gene encodes the enzyme sulfamidase; one of several enzymes involved in the lysosomal degradation of heparan sulfate. Mutations in this gene are associated with the lysosomal storage disease mucopolysaccaridosis IIIA, also known as Sanfilippo syndrome A, which results from impaired degradation of heparan sulfate. Transcripts of varying sizes have been reported but their biological validity has not been determined. [provided by RefSeq, Jun 2017]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BP6: Variant 17-80206819-A-C is Benign according to our data. Variant chr17-80206819-A-C is described in ClinVar as [Benign]. Clinvar id is 1246193.Status of the report is criteria_provided_single_submitter, 1 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	UniProt
CARD14	NM_001366385.1	c.2692-151A>C		intron_variant		ENST00000648509.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CARD14	ENST00000648509.2	c.2692-151A>C		intron_variant			NM_001366385.1	P1

Frequencies

GnomAD3 genomes AF: 0.486 AC: 73900 AN: 151948 Hom.: 19062 Cov.: 33

Gnomad AFR AF: 0.307

Gnomad AMI AF: 0.662

Gnomad AMR AF: 0.439

Gnomad ASJ AF: 0.549

Gnomad EAS AF: 0.572

Gnomad SAS AF: 0.495

Gnomad FIN AF: 0.548

Gnomad MID AF: 0.494

Gnomad NFE AF: 0.584

Gnomad OTH AF: 0.486

GnomAD4 exome AF: 0.567 AC: 167814 AN: 295878 Hom.: 48480 Cov.: 3 AF XY: 0.567 AC XY: 86933 AN XY: 153330

Gnomad4 AFR exome AF: 0.318

Gnomad4 AMR exome AF: 0.417

Gnomad4 ASJ exome AF: 0.546

Gnomad4 EAS exome AF: 0.677

Gnomad4 SAS exome AF: 0.511

Gnomad4 FIN exome AF: 0.545

Gnomad4 NFE exome AF: 0.584

Gnomad4 OTH exome AF: 0.535

GnomAD4 genome AF: 0.486 AC: 73919 AN: 152066 Hom.: 19060 Cov.: 33 AF XY: 0.486 AC XY: 36128 AN XY: 74322

Gnomad4 AFR AF: 0.307

Gnomad4 AMR AF: 0.438

Gnomad4 ASJ AF: 0.549

Gnomad4 EAS AF: 0.572

Gnomad4 SAS AF: 0.496

Gnomad4 FIN AF: 0.548

Gnomad4 NFE AF: 0.584

Gnomad4 OTH AF: 0.485

Alfa AF: 0.563 Hom.: 35445

Bravo AF: 0.467

Asia WGS AF: 0.521 AC: 1811 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 09, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
Cadd	Benign	1.5
Dann	Benign	0.73

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: rs4889998; hg19: chr17-78180618; COSMIC: COSV58339408; COSMIC: COSV58339408;