rs884367

Variant names:

• chr17-5583844-C-A
• rs884367
• NM_033004.4:c.114G>T

Your query was ambiguous. Multiple possible variants found:

• chr17-5583844-C-A
• chr17-5583844-C-G
• chr17-5583844-C-T

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_Strong BP7

The NM_033004.4(NLRP1):​c.114G>T​(p.Ser38Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000423 in 1,417,452 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. S38S) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000042 (0 hom.)
• Consequence: NLRP1 NM_033004.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -5.04
• Publications: 22 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):

• autoinflammation with arthritis and dyskeratosis

  Inheritance: AR, SD Classification: STRONG, LIMITED Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• corneal intraepithelial dyskeratosis-palmoplantar hyperkeratosis-laryngeal dyskeratosis syndrome

  Inheritance: SD, AD Classification: STRONG, MODERATE, SUPPORTIVE, LIMITED Submitted by: Ambry Genetics, G2P, Orphanet, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP7: Synonymous conserved (PhyloP=-5.04 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033004.4. 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_033004.4	MANE Select	c.114G>T	p.Ser38Ser	synonymous	Exon 1 of 17	NP_127497.1	Q9C000-1
	NLRP1	NM_033006.4		c.114G>T	p.Ser38Ser	synonymous	Exon 1 of 16	NP_127499.1	Q9C000-4
	NLRP1	NM_014922.5		c.114G>T	p.Ser38Ser	synonymous	Exon 1 of 16	NP_055737.1	Q9C000-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NLRP1	ENST00000572272.6	TSL:1 MANE Select	c.114G>T	p.Ser38Ser	synonymous	Exon 1 of 17	ENSP00000460475.1	Q9C000-1
	NLRP1	ENST00000354411.8	TSL:1	c.114G>T	p.Ser38Ser	synonymous	Exon 1 of 16	ENSP00000346390.3	Q9C000-4
	NLRP1	ENST00000269280.9	TSL:1	c.114G>T	p.Ser38Ser	synonymous	Exon 2 of 17	ENSP00000269280.4	Q9C000-2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000545 AC: 1 AN: 183436 AF XY: 0.0000102

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000423 AC: 6 AN: 1417452 Hom.: 0 Cov.: 34 AF XY: 0.00000713 AC XY: 5 AN XY: 701094

African (AFR) AF: 0.00 AC: 0 AN: 32670

American (AMR) AF: 0.00 AC: 0 AN: 38462

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25418

East Asian (EAS) AF: 0.00 AC: 0 AN: 37464

South Asian (SAS) AF: 0.0000617 AC: 5 AN: 81092

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50376

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5702

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1087622

Other (OTH) AF: 0.0000171 AC: 1 AN: 58646

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	0.45
DANN	Benign	0.57
PhyloP100		-5.0
PromoterAI		-0.0062	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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

Other links and lift over

dbSNP: rs884367; hg19: chr17-5487164;