11-105100582-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NR_172520.1(CARD17P):n.250T>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00098 in 1,613,856 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 Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00060 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0010 (0 hom.)
• Consequence: CARD17P NR_172520.1 non_coding_transcript_exon
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.171

Genes affected

CARD17P (HGNC:33827): (caspase recruitment domain family member 17, pseudogene) Enables caspase binding activity and identical protein binding activity. Involved in cellular response to lipopolysaccharide and negative regulation of interleukin-1 beta production. Part of protein-containing complex. [provided by Alliance of Genome Resources, Apr 2022]

(HGNC:):

CARD16 (HGNC:33701): (caspase recruitment domain family member 16) Enables several functions, including CARD domain binding activity; cysteine-type endopeptidase inhibitor activity; and enzyme binding activity. Involved in several processes, including negative regulation of cysteine-type endopeptidase activity; regulation of gene expression; and regulation of signal transduction. Part of protease inhibitor complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09402147).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CARD17P	NR_172520.1	n.250T>C		non_coding_transcript_exon_variant	2/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CARD17P	ENST00000638172.1	n.205T>C		non_coding_transcript_exon_variant	2/9
	ENST00000638998.1	n.222T>C		non_coding_transcript_exon_variant	2/4	1
CARD16	ENST00000525374.1	n.24+826T>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.000605 AC: 92 AN: 152148 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000314

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000943

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000985

Gnomad OTH AF: 0.000479

GnomAD3 exomes AF: 0.000426 AC: 107 AN: 251272 Hom.: 0 AF XY: 0.000427 AC XY: 58 AN XY: 135796

Gnomad AFR exome AF: 0.0000615

Gnomad AMR exome AF: 0.0000579

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000898

Gnomad OTH exome AF: 0.000326

GnomAD4 exome AF: 0.00102 AC: 1490 AN: 1461590 Hom.: 0 Cov.: 33 AF XY: 0.00104 AC XY: 756 AN XY: 727112

Gnomad4 AFR exome AF: 0.000149

Gnomad4 AMR exome AF: 0.000134

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0000187

Gnomad4 NFE exome AF: 0.00127

Gnomad4 OTH exome AF: 0.00114

GnomAD4 genome AF: 0.000604 AC: 92 AN: 152266 Hom.: 0 Cov.: 32 AF XY: 0.000470 AC XY: 35 AN XY: 74438

Gnomad4 AFR AF: 0.000313

Gnomad4 AMR AF: 0.000654

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.0000943

Gnomad4 NFE AF: 0.000985

Gnomad4 OTH AF: 0.000474

Alfa AF: 0.000782 Hom.: 0

Bravo AF: 0.000695

TwinsUK AF: 0.00108 AC: 4

ALSPAC AF: 0.00234 AC: 9

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.00151 AC: 13

ExAC AF: 0.000362 AC: 44

EpiCase AF: 0.000873

EpiControl AF: 0.00101

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 08, 2022

The c.205T>C (p.C69R) alteration is located in exon 2 (coding exon 2) of the CARD17 gene. This alteration results from a T to C substitution at nucleotide position 205, causing the cysteine (C) at amino acid position 69 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.66
BayesDel_addAF	Benign	-0.48	T
BayesDel_noAF	Benign	-0.47
Cadd	Benign	0.62
Dann	Benign	0.61
DEOGEN2	Benign	0.066	T
Eigen	Benign	-0.83
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.022	N
LIST_S2	Uncertain	0.86	D
M_CAP	Benign	0.0024	T
MetaRNN	Benign	0.094	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Pathogenic	2.9	M
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.42	T
PROVEAN	Pathogenic	-7.3	D
REVEL	Benign	0.12
Sift	Benign	0.094	T
Sift4G	Uncertain	0.012	D
Polyphen		0.92	P
Vest4		0.52
MVP		0.20
MPC		0.0028
ClinPred		0.30	T
GERP RS		-5.7
Varity_R		0.46
gMVP		0.43

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs141250558; hg19: chr11-104971309; COSMIC: COSV65214806;