rs200394665

Positions:

• chr17-80205667-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001366385.1(CARD14):​c.2691+15G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00121 in 1,537,404 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0012 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0012 (7 hom.)
• Consequence: CARD14 NM_001366385.1 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -1.43

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]

ENSG00000262580 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BP6: Variant 17-80205667-G-A is Benign according to our data. Variant chr17-80205667-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 402488.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-80205667-G-A is described in Lovd as [Likely_benign].
• BS1: Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00122 (186/152254) while in subpopulation AMR AF= 0.00353 (54/15292). AF 95% confidence interval is 0.00278. There are 0 homozygotes in gnomad4. There are 90 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 186 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CARD14	NM_001366385.1	c.2691+15G>A		intron_variant		ENST00000648509.2	NP_001353314.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CARD14	ENST00000648509.2	c.2691+15G>A		intron_variant			NM_001366385.1	ENSP00000498071.1

Frequencies

GnomAD3 genomes AF: 0.00122 AC: 186 AN: 152136 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000338

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00354

Gnomad ASJ AF: 0.00806

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00269

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000970

Gnomad OTH AF: 0.00383

GnomAD3 exomes AF: 0.00221 AC: 323 AN: 146448 Hom.: 2 AF XY: 0.00249 AC XY: 188 AN XY: 75504

Gnomad AFR exome AF: 0.000100

Gnomad AMR exome AF: 0.00395

Gnomad ASJ exome AF: 0.00879

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00526

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00119

Gnomad OTH exome AF: 0.00377

GnomAD4 exome AF: 0.00121 AC: 1676 AN: 1385150 Hom.: 7 Cov.: 36 AF XY: 0.00133 AC XY: 907 AN XY: 681716

Gnomad4 AFR exome AF: 0.000280

Gnomad4 AMR exome AF: 0.00367

Gnomad4 ASJ exome AF: 0.00644

Gnomad4 EAS exome AF: 0.0000269

Gnomad4 SAS exome AF: 0.00463

Gnomad4 FIN exome AF: 0.0000624

Gnomad4 NFE exome AF: 0.000783

Gnomad4 OTH exome AF: 0.00263

GnomAD4 genome AF: 0.00122 AC: 186 AN: 152254 Hom.: 0 Cov.: 32 AF XY: 0.00121 AC XY: 90 AN XY: 74442

Gnomad4 AFR AF: 0.000337

Gnomad4 AMR AF: 0.00353

Gnomad4 ASJ AF: 0.00806

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00270

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000971

Gnomad4 OTH AF: 0.00379

Alfa AF: 0.00274 Hom.: 1

Bravo AF: 0.00153

Asia WGS AF: 0.00115 AC: 4 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 29, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency, does not alter splice consensus -

Pityriasis rubra pilaris;C1864497:Psoriasis 2 Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 26, 2024

- -

not provided Benign:1

Likely benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.5
DANN	Benign	0.58

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: rs200394665; hg19: chr17-78179466;