rs62074378

Variant names:

• chr17-80195205-G-A
• rs62074378
• NM_001366385.1:c.1371G>A

Your query was ambiguous. Multiple possible variants found:

• chr17-80195205-G-A
• chr17-80195205-G-C

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.1371G>A​(p.Ser457Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0416 in 1,608,020 control chromosomes in the GnomAD database, including 1,584 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. S457S) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.031 (101 hom., cov: 32)
  • Exomes 𝑓: 0.043 (1483 hom.)
• Consequence: CARD14 NM_001366385.1 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -2.07

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=-0.91).
• BP6: Variant 17-80195205-G-A is Benign according to our data. Variant chr17-80195205-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 458086.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-2.07 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0312 (4752/152242) while in subpopulation NFE AF= 0.0462 (3141/67990). AF 95% confidence interval is 0.0448. There are 101 homozygotes in gnomad4. There are 2276 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 4752 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CARD14	NM_001366385.1	c.1371G>A	p.Ser457Ser	synonymous_variant	Exon 13 of 24	ENST00000648509.2	NP_001353314.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CARD14	ENST00000648509.2	c.1371G>A	p.Ser457Ser	synonymous_variant	Exon 13 of 24		NM_001366385.1	ENSP00000498071.1

Frequencies

GnomAD3 genomes AF: 0.0313 AC: 4755 AN: 152124 Hom.: 102 Cov.: 32

Gnomad AFR AF: 0.00922

Gnomad AMI AF: 0.0143

Gnomad AMR AF: 0.0300

Gnomad ASJ AF: 0.0291

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0343

Gnomad FIN AF: 0.0390

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0462

Gnomad OTH AF: 0.0335

GnomAD3 exomes AF: 0.0339 AC: 8355 AN: 246688 Hom.: 165 AF XY: 0.0350 AC XY: 4681 AN XY: 133760

Gnomad AFR exome AF: 0.00947

Gnomad AMR exome AF: 0.0181

Gnomad ASJ exome AF: 0.0365

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0324

Gnomad FIN exome AF: 0.0373

Gnomad NFE exome AF: 0.0474

Gnomad OTH exome AF: 0.0361

GnomAD4 exome AF: 0.0427 AC: 62161 AN: 1455778 Hom.: 1483 Cov.: 31 AF XY: 0.0425 AC XY: 30760 AN XY: 723478

Gnomad4 AFR exome AF: 0.00901

Gnomad4 AMR exome AF: 0.0191

Gnomad4 ASJ exome AF: 0.0346

Gnomad4 EAS exome AF: 0.000126

Gnomad4 SAS exome AF: 0.0335

Gnomad4 FIN exome AF: 0.0376

Gnomad4 NFE exome AF: 0.0476

Gnomad4 OTH exome AF: 0.0374

GnomAD4 genome AF: 0.0312 AC: 4752 AN: 152242 Hom.: 101 Cov.: 32 AF XY: 0.0306 AC XY: 2276 AN XY: 74442

Gnomad4 AFR AF: 0.00920

Gnomad4 AMR AF: 0.0300

Gnomad4 ASJ AF: 0.0291

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0337

Gnomad4 FIN AF: 0.0390

Gnomad4 NFE AF: 0.0462

Gnomad4 OTH AF: 0.0331

Alfa AF: 0.0279 Hom.: 31

Bravo AF: 0.0294

Asia WGS AF: 0.0150 AC: 54 AN: 3478

EpiCase AF: 0.0458

EpiControl AF: 0.0491

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jul 09, 2018

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Pityriasis rubra pilaris;C1864497:Psoriasis 2 Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Autoinflammatory syndrome Benign:1

Jan 22, 2022

Genome Diagnostics Laboratory, The Hospital for Sick Children

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.1
DANN	Benign	0.41

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs62074378; hg19: chr17-78169004;