rs11653414

Variant names:

• chr17-5511718-A-C
• rs11653414
• ENST00000574512.1:n.821-5741T>G

Variant summary

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

The NM_001033053.3(NLRP1):​c.4069+6028T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.165 in 142,906 control chromosomes in the GnomAD database, including 3,623 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 0.17 (3623 hom., cov: 31)
• Consequence: NLRP1 NM_001033053.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.42
• 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

LOC101928044 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.09).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.423 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001033053.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NLRP1	NM_001033053.3		c.4069+6028T>G		intron	N/A	NP_001028225.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NLRP1	ENST00000574512.1	TSL:1	n.821-5741T>G		intron	N/A
	NLRP1	ENST00000699613.1		c.4102+3755T>G		intron	N/A	ENSP00000514477.1
	NLRP1	ENST00000262467.11	TSL:5	c.4069+6028T>G		intron	N/A	ENSP00000262467.5

Frequencies

GnomAD3 genomes AF: 0.165 AC: 23545 AN: 142808 Hom.: 3605 Cov.: 31

Gnomad AFR AF: 0.428

Gnomad AMI AF: 0.0302

Gnomad AMR AF: 0.106

Gnomad ASJ AF: 0.0826

Gnomad EAS AF: 0.0784

Gnomad SAS AF: 0.0400

Gnomad FIN AF: 0.0452

Gnomad MID AF: 0.107

Gnomad NFE AF: 0.0598

Gnomad OTH AF: 0.158

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

GnomAD4 genome AF: 0.165 AC: 23602 AN: 142906 Hom.: 3623 Cov.: 31 AF XY: 0.161 AC XY: 11149 AN XY: 69110

African (AFR) AF: 0.429 AC: 16598 AN: 38726

American (AMR) AF: 0.105 AC: 1515 AN: 14366

Ashkenazi Jewish (ASJ) AF: 0.0826 AC: 282 AN: 3414

East Asian (EAS) AF: 0.0784 AC: 315 AN: 4016

South Asian (SAS) AF: 0.0393 AC: 166 AN: 4224

European-Finnish (FIN) AF: 0.0452 AC: 416 AN: 9210

Middle Eastern (MID) AF: 0.115 AC: 32 AN: 278

European-Non Finnish (NFE) AF: 0.0599 AC: 3940 AN: 65826

Other (OTH) AF: 0.157 AC: 312 AN: 1984

Alfa AF: 0.117 Hom.: 387

Bravo AF: 0.173

Asia WGS AF: 0.0760 AC: 264 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.43
DANN	Benign	0.28
PhyloP100		-3.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs11653414; hg19: chr17-5415038;