rs144207494

Positions:

• chr17-80189869-G-A
• chr17-80189869-G-T

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.960G>A​(p.Glu320=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00038 in 1,595,814 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00087 (3 hom., cov: 32)
  • Exomes 𝑓: 0.00033 (9 hom.)
• Consequence: CARD14 NM_001366385.1 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.0150

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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BP6: Variant 17-80189869-G-A is Benign according to our data. Variant chr17-80189869-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 458110.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.015 with no splicing effect.
• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.000867 (132/152290) while in subpopulation EAS AF= 0.0196 (101/5166). AF 95% confidence interval is 0.0165. There are 3 homozygotes in gnomad4. There are 71 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 132 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CARD14	NM_001366385.1	c.960G>A	p.Glu320=	synonymous_variant	9/24	ENST00000648509.2	NP_001353314.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CARD14	ENST00000648509.2	c.960G>A	p.Glu320=	synonymous_variant	9/24		NM_001366385.1	ENSP00000498071	P1

Frequencies

GnomAD3 genomes AF: 0.000867 AC: 132 AN: 152172 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.000217

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000982

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0195

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00143

GnomAD3 exomes AF: 0.00136 AC: 311 AN: 229062 Hom.: 6 AF XY: 0.00113 AC XY: 142 AN XY: 125620

Gnomad AFR exome AF: 0.000214

Gnomad AMR exome AF: 0.000195

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0184

Gnomad SAS exome AF: 0.000344

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00128

GnomAD4 exome AF: 0.000329 AC: 475 AN: 1443524 Hom.: 9 Cov.: 31 AF XY: 0.000298 AC XY: 214 AN XY: 718414

Gnomad4 AFR exome AF: 0.0000946

Gnomad4 AMR exome AF: 0.000168

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00788

Gnomad4 SAS exome AF: 0.000403

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000634

Gnomad4 OTH exome AF: 0.00215

GnomAD4 genome AF: 0.000867 AC: 132 AN: 152290 Hom.: 3 Cov.: 32 AF XY: 0.000954 AC XY: 71 AN XY: 74458

Gnomad4 AFR AF: 0.000217

Gnomad4 AMR AF: 0.000980

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.0196

Gnomad4 SAS AF: 0.000415

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000294

Gnomad4 OTH AF: 0.00142

Alfa AF: 0.000354 Hom.: 0

Bravo AF: 0.000914

Asia WGS AF: 0.0110 AC: 39 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Pityriasis rubra pilaris;C1864497:Psoriasis 2 Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago	Oct 28, 2022	This variant has not been reported in the literature but is present in the Genome Aggregation Database (Highest reported MAF 0.09% (15/15282) (https://gnomad.broadinstitute.org/variant/17-80189869-G-A?dataset=gnomad_r3). This variant is present in ClinVar, with multiple labs classifying this variant as Likely Benign or Benign (Variation ID:458110). Evolutionary conservation and computational predictive tools for this variant are limited or unavailable. Of note, this variant is a silent variant and does not change the amino acid, reducing the probability that this variant is disease causing. In summary, data on this variant suggests that this variant does not cause disease but requires further evidence. Therefore, this variant is classified as likely benign. -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 19, 2024	- -

Autoinflammatory syndrome Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Genome Diagnostics Laboratory, The Hospital for Sick Children

Nov 25, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	4.0
DANN	Benign	0.45

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: rs144207494; hg19: chr17-78163668;