chr11-105100615-G-A

Position:

• chr11-105100615-G-A

Variant summary

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

The NR_172520.1(CARD17P):​n.217C>T 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 0.000000684 in 1,461,638 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: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CARD17P NR_172520.1 non_coding_transcript_exon
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.411

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=0.16238704).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CARD17P	NR_172520.1	n.217C>T		non_coding_transcript_exon_variant	2/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CARD17P	ENST00000638172.1	n.172C>T		non_coding_transcript_exon_variant	2/9
	ENST00000638998.1	n.189C>T		non_coding_transcript_exon_variant	2/4	1
CARD16	ENST00000525374.1	n.24+793C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461638 Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1 AN XY: 727134

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

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

Oct 10, 2023

The c.172C>T (p.L58F) alteration is located in exon 2 (coding exon 2) of the CARD17 gene. This alteration results from a C to T substitution at nucleotide position 172, causing the leucine (L) at amino acid position 58 to be replaced by a phenylalanine (F). 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	Benign	0.18
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	0.13
DANN	Benign	0.86
DEOGEN2	Benign	0.056	T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.016	N
LIST_S2	Benign	0.31	T
M_CAP	Benign	0.0023	T
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.1	L
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.036
Sift	Uncertain	0.0040	D
Sift4G	Benign	0.10	T
Polyphen		0.013	B
Vest4		0.24
MutPred		0.66		Gain of catalytic residue at L58 (P = 0.0822);
MVP		0.048
MPC		0.0019
ClinPred		0.079	T
GERP RS		-5.8
Varity_R		0.12
gMVP		0.21

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-104971342;