rs78569961

chr17-80208183-G-A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_001366385.1(CARD14):c.2853G>A(p.Glu951=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00275 in 1,550,800 control chromosomes in the GnomAD database, including 88 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.015 (48 hom., cov: 33)
  • Exomes 𝑓: 0.0015 (40 hom.)
• Consequence: CARD14 NM_001366385.1 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.811

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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BP6: Variant 17-80208183-G-A is Benign according to our data. Variant chr17-80208183-G-A is described in ClinVar as [Benign]. Clinvar id is 458100.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.811 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0146 (2229/152360) while in subpopulation AFR AF= 0.0505 (2098/41582). AF 95% confidence interval is 0.0487. There are 48 homozygotes in gnomad4. There are 1087 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High AC in GnomAd at 2227 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CARD14	NM_001366385.1	c.2853G>A	p.Glu951=	synonymous_variant	24/24	ENST00000648509.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CARD14	ENST00000648509.2	c.2853G>A	p.Glu951=	synonymous_variant	24/24		NM_001366385.1	P1

Frequencies

GnomAD3 genomes AF: 0.0146 AC: 2227 AN: 152242 Hom.: 48 Cov.: 33

Gnomad AFR AF: 0.0506

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00595

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000162

Gnomad OTH AF: 0.0124

GnomAD3 exomes AF: 0.00354 AC: 557 AN: 157124 Hom.: 12 AF XY: 0.00273 AC XY: 226 AN XY: 82894

Gnomad AFR exome AF: 0.0512

Gnomad AMR exome AF: 0.00287

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000876

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000182

Gnomad OTH exome AF: 0.00249

GnomAD4 exome AF: 0.00145 AC: 2032 AN: 1398440 Hom.: 40 Cov.: 32 AF XY: 0.00122 AC XY: 844 AN XY: 689682

Gnomad4 AFR exome AF: 0.0504

Gnomad4 AMR exome AF: 0.00286

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000757

Gnomad4 FIN exome AF: 0.0000207

Gnomad4 NFE exome AF: 0.000103

Gnomad4 OTH exome AF: 0.00333

GnomAD4 genome AF: 0.0146 AC: 2229 AN: 152360 Hom.: 48 Cov.: 33 AF XY: 0.0146 AC XY: 1087 AN XY: 74516

Gnomad4 AFR AF: 0.0505

Gnomad4 AMR AF: 0.00594

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000621

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000162

Gnomad4 OTH AF: 0.0123

Alfa AF: 0.00700 Hom.: 9

Bravo AF: 0.0166

Asia WGS AF: 0.00260 AC: 10 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Pityriasis rubra pilaris;C1864497:Psoriasis 2 Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 29, 2024

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 09, 2018

- -

Autoinflammatory syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome Diagnostics Laboratory, The Hospital for Sick Children

Feb 25, 2022

- -

CARD14-related condition Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

May 22, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
Cadd	Benign	3.9
Dann	Benign	0.79

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs78569961; hg19: chr17-78181982;