17-5615686-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000576905.6(NLRP1):c.-355+3645T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.412 in 152,048 control chromosomes in the GnomAD database, including 13,284 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 0.41 (13284 hom., cov: 32)
• Consequence: NLRP1 ENST00000576905.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.23

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.451 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NLRP1	ENST00000576905.6	c.-355+3645T>C		intron_variant		4
NLRP1	ENST00000572143.2	c.-544+3645T>C		intron_variant, NMD_transcript_variant		4
NLRP1	ENST00000699639.1	n.84+3645T>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.412 AC: 62532 AN: 151928 Hom.: 13259 Cov.: 32

Gnomad AFR AF: 0.347

Gnomad AMI AF: 0.584

Gnomad AMR AF: 0.432

Gnomad ASJ AF: 0.461

Gnomad EAS AF: 0.177

Gnomad SAS AF: 0.402

Gnomad FIN AF: 0.439

Gnomad MID AF: 0.430

Gnomad NFE AF: 0.456

Gnomad OTH AF: 0.412

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

GnomAD4 genome AF: 0.412 AC: 62612 AN: 152048 Hom.: 13284 Cov.: 32 AF XY: 0.411 AC XY: 30537 AN XY: 74302

Gnomad4 AFR AF: 0.347

Gnomad4 AMR AF: 0.432

Gnomad4 ASJ AF: 0.461

Gnomad4 EAS AF: 0.179

Gnomad4 SAS AF: 0.404

Gnomad4 FIN AF: 0.439

Gnomad4 NFE AF: 0.456

Gnomad4 OTH AF: 0.419

Alfa AF: 0.427 Hom.: 1705

Bravo AF: 0.408

Asia WGS AF: 0.344 AC: 1197 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	14
Dann	Benign	0.71

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2670660; hg19: chr17-5519006;