rs925596

Variant names:

• chr17-5584779-G-A
• rs925596
• ENST00000576905.6:c.-354-279C>T

Your query was ambiguous. Multiple possible variants found:

• chr17-5584779-G-A
• chr17-5584779-G-C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000576905.6(NLRP1):​c.-354-279C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.934 in 152,292 control chromosomes in the GnomAD database, including 66,466 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.93 (66466 hom., cov: 33)
• Consequence: NLRP1 ENST00000576905.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.398
• Publications: 4 publications found

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]

NLRP1 Gene-Disease associations (from GenCC):

• corneal intraepithelial dyskeratosis-palmoplantar hyperkeratosis-laryngeal dyskeratosis syndrome

  Inheritance: AD, SD Classification: STRONG, MODERATE, SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, G2P, Ambry Genetics
• autoinflammation with arthritis and dyskeratosis

  Inheritance: AR, SD Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NLRP1	ENST00000576905.6	c.-354-279C>T		intron_variant	Intron 1 of 17	4		ENSP00000458303.2
NLRP1	ENST00000572143.2	n.-543-279C>T		intron_variant	Intron 1 of 17	4		ENSP00000514476.1

Frequencies

GnomAD3 genomes AF: 0.933 AC: 142047 AN: 152174 Hom.: 66405 Cov.: 33

Gnomad AFR AF: 0.980

Gnomad AMI AF: 0.938

Gnomad AMR AF: 0.930

Gnomad ASJ AF: 0.931

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.981

Gnomad FIN AF: 0.938

Gnomad MID AF: 0.946

Gnomad NFE AF: 0.897

Gnomad OTH AF: 0.921

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.934 AC: 142169 AN: 152292 Hom.: 66466 Cov.: 33 AF XY: 0.936 AC XY: 69718 AN XY: 74470

African (AFR) AF: 0.980 AC: 40740 AN: 41566

American (AMR) AF: 0.930 AC: 14236 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.931 AC: 3230 AN: 3470

East Asian (EAS) AF: 1.00 AC: 5163 AN: 5164

South Asian (SAS) AF: 0.981 AC: 4736 AN: 4828

European-Finnish (FIN) AF: 0.938 AC: 9958 AN: 10618

Middle Eastern (MID) AF: 0.949 AC: 279 AN: 294

European-Non Finnish (NFE) AF: 0.897 AC: 61022 AN: 68024

Other (OTH) AF: 0.922 AC: 1950 AN: 2114

Alfa AF: 0.907 Hom.: 23956

Bravo AF: 0.935

Asia WGS AF: 0.989 AC: 3440 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.5
DANN	Benign	0.72
PhyloP100		-0.40
PromoterAI		-0.063	Neutral

Splicing

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

Other links and lift over

dbSNP: rs925596; hg19: chr17-5488099;