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GeneBe

17-5514829-C-T

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7

The NM_033004.4(NLRP1):c.4347G>A(p.Lys1449=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000201 in 1,614,090 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00019 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00020 ( 1 hom. )

Consequence

NLRP1
NM_033004.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.475
Variant links:
Genes affected
NLRP1 (HGNC:14374): (NLR family pyrin domain containing 1) This gene encodes a member of the Ced-4 family of apoptosis proteins. Ced-family members contain a caspase recruitment domain (CARD) and are known to be key mediators of programmed cell death. The encoded protein contains a distinct N-terminal pyrin-like motif, which is possibly involved in protein-protein interactions. This protein interacts strongly with caspase 2 and weakly with caspase 9. Overexpression of this gene was demonstrated to induce apoptosis in cells. Multiple alternatively spliced transcript variants encoding distinct isoforms have been found for this gene, but the biological validity of some variants has not been determined. [provided by RefSeq, Jul 2008]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

PM2
?
    PM2 - Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
Very rare variant in population databases, with high coverage;
BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.52).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 17-5514829-C-T is Benign according to our data. Variant chr17-5514829-C-T is described in ClinVar as [Benign]. Clinvar id is 1566292.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=0.475 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
NLRP1NM_033004.4 linkuse as main transcriptc.4347G>A p.Lys1449= synonymous_variant 17/17 ENST00000572272.6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
NLRP1ENST00000572272.6 linkuse as main transcriptc.4347G>A p.Lys1449= synonymous_variant 17/171 NM_033004.4 P2Q9C000-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000191
AC:
29
AN:
152082
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00375
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00166
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000118
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000321
AC:
80
AN:
249570
Hom.:
1
AF XY:
0.000362
AC XY:
49
AN XY:
135404
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000290
Gnomad ASJ exome
AF:
0.00328
Gnomad EAS exome
AF:
0.000111
Gnomad SAS exome
AF:
0.000850
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000115
Gnomad OTH exome
AF:
0.000824
GnomAD4 exome
AF:
0.000202
AC:
296
AN:
1461890
Hom.:
1
Cov.:
32
AF XY:
0.000253
AC XY:
184
AN XY:
727246
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00394
Gnomad4 EAS exome
AF:
0.000101
Gnomad4 SAS exome
AF:
0.00107
Gnomad4 FIN exome
AF:
0.0000187
Gnomad4 NFE exome
AF:
0.0000585
Gnomad4 OTH exome
AF:
0.000497
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000191
AC:
29
AN:
152200
Hom.:
0
Cov.:
32
AF XY:
0.000242
AC XY:
18
AN XY:
74412
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00375
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00166
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000118
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000329
Hom.:
0
Bravo
AF:
0.000155
Asia WGS
AF:
0.00115
AC:
4
AN:
3478
EpiCase
AF:
0.0000545
EpiControl
AF:
0.0000593

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeJan 19, 2024- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.52
Cadd
Benign
7.9
Dann
Benign
0.68

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs199931784; hg19: chr17-5418149; COSMIC: COSV99335149; COSMIC: COSV99335149; API