17-5517008-C-T

Variant names:

• chr17-5517008-C-T
• rs6502867
• NM_033004.4:c.4057+738G>A

Variant summary

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

The NM_033004.4(NLRP1):​c.4057+738G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.819 in 152,230 control chromosomes in the GnomAD database, including 51,387 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 0.82 (51387 hom., cov: 32)
• Consequence: NLRP1 NM_033004.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.295

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=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.945 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NLRP1	NM_033004.4	c.4057+738G>A		intron_variant	Intron 15 of 16	ENST00000572272.6	NP_127497.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NLRP1	ENST00000572272.6	c.4057+738G>A		intron_variant	Intron 15 of 16	1	NM_033004.4	ENSP00000460475.1

Frequencies

GnomAD3 genomes AF: 0.818 AC: 124483 AN: 152112 Hom.: 51327 Cov.: 32

Gnomad AFR AF: 0.911

Gnomad AMI AF: 0.800

Gnomad AMR AF: 0.788

Gnomad ASJ AF: 0.709

Gnomad EAS AF: 0.968

Gnomad SAS AF: 0.837

Gnomad FIN AF: 0.829

Gnomad MID AF: 0.677

Gnomad NFE AF: 0.762

Gnomad OTH AF: 0.776

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

GnomAD4 genome AF: 0.819 AC: 124607 AN: 152230 Hom.: 51387 Cov.: 32 AF XY: 0.822 AC XY: 61223 AN XY: 74436

Gnomad4 AFR AF: 0.911

Gnomad4 AMR AF: 0.788

Gnomad4 ASJ AF: 0.709

Gnomad4 EAS AF: 0.968

Gnomad4 SAS AF: 0.836

Gnomad4 FIN AF: 0.829

Gnomad4 NFE AF: 0.762

Gnomad4 OTH AF: 0.779

Alfa AF: 0.767 Hom.: 59852

Bravo AF: 0.818

Asia WGS AF: 0.899 AC: 3126 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.6
DANN	Benign	0.64

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

Other links and lift over

dbSNP: rs6502867; hg19: chr17-5420328; COSMIC: COSV52561912; COSMIC: COSV52561912;