chr17-80188529-G-T

Variant names:

• chr17-80188529-G-T
• rs150424747
• NM_001366385.1:c.828G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BP6_Moderate BP7 BS1 BS2_Supporting

The NM_001366385.1(CARD14):​c.828G>T​(p.Ser276Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000659 in 1,365,072 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. S276S) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000066 (0 hom.)
• Consequence: CARD14 NM_001366385.1 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -5.22
• Publications: 1 publications found

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]

CARD14 Gene-Disease associations (from GenCC):

• familial pityriasis rubra pilaris

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Orphanet, Genomics England PanelApp
• psoriasis 2

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae), Genomics England PanelApp

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 17-80188529-G-T is Benign according to our data. Variant chr17-80188529-G-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2930620.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-5.22 with no splicing effect.
• BS1: Variant frequency is greater than expected in population amr. GnomAdExome4 allele frequency = 0.00000659 (9/1365072) while in subpopulation AMR AF = 0.000282 (9/31886). AF 95% confidence interval is 0.000147. There are 0 homozygotes in GnomAdExome4. There are 3 alleles in the male GnomAdExome4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High AC in GnomAdExome4 at 9 AD gene. Variant has AC lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001366385.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CARD14	NM_001366385.1	MANE Select	c.828G>T	p.Ser276Ser	synonymous	Exon 8 of 24	NP_001353314.1
	CARD14	NM_024110.4		c.828G>T	p.Ser276Ser	synonymous	Exon 5 of 21	NP_077015.2
	CARD14	NM_001257970.1		c.828G>T	p.Ser276Ser	synonymous	Exon 5 of 15	NP_001244899.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CARD14	ENST00000648509.2	MANE Select	c.828G>T	p.Ser276Ser	synonymous	Exon 8 of 24	ENSP00000498071.1
	CARD14	ENST00000344227.6	TSL:1	c.828G>T	p.Ser276Ser	synonymous	Exon 5 of 21	ENSP00000344549.2
	CARD14	ENST00000570421.5	TSL:1	c.828G>T	p.Ser276Ser	synonymous	Exon 5 of 15	ENSP00000461806.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.0000510 AC: 9 AN: 176478 AF XY: 0.0000318

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000416

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000659 AC: 9 AN: 1365072 Hom.: 0 Cov.: 31 AF XY: 0.00000447 AC XY: 3 AN XY: 671660

African (AFR) AF: 0.00 AC: 0 AN: 29810

American (AMR) AF: 0.000282 AC: 9 AN: 31886

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21378

East Asian (EAS) AF: 0.00 AC: 0 AN: 35390

South Asian (SAS) AF: 0.00 AC: 0 AN: 71472

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50832

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4780

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1063338

Other (OTH) AF: 0.00 AC: 0 AN: 56186

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000189

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Pityriasis rubra pilaris;C1864497:Psoriasis 2 Benign:1

Jul 19, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.13
DANN	Benign	0.59
PhyloP100		-5.2

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

Other links and lift over

dbSNP: rs150424747; hg19: chr17-78162328;