rs17608620

chr19-56011557-C-T

Variant summary

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

The NM_153447.4(NLRP5):c.508+2704C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.339 in 151,850 control chromosomes in the GnomAD database, including 9,261 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 0.34 (9261 hom., cov: 31)
• Consequence: NLRP5 NM_153447.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.763

Genes affected

NLRP5 (HGNC:21269): (NLR family pyrin domain containing 5) The protein encoded by this gene belongs to the NALP protein family. Members of the NALP protein family typically contain a NACHT domain, a NACHT-associated domain (NAD), a C-terminal leucine-rich repeat (LRR) region, and an N-terminal pyrin domain (PYD). Expression of this gene is restricted to the oocyte. A mouse gene that encodes a maternal oocyte protein, similar to this encoded protein, is required for normal early embryogenesis. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.401 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NLRP5	NM_153447.4	c.508+2704C>T		intron_variant		ENST00000390649.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NLRP5	ENST00000390649.8	c.508+2704C>T		intron_variant		1	NM_153447.4	P1
NLRP5	ENST00000597673.1	c.427+2704C>T		intron_variant, NMD_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.339 AC: 51377 AN: 151732 Hom.: 9263 Cov.: 31

Gnomad AFR AF: 0.225

Gnomad AMI AF: 0.351

Gnomad AMR AF: 0.388

Gnomad ASJ AF: 0.332

Gnomad EAS AF: 0.107

Gnomad SAS AF: 0.339

Gnomad FIN AF: 0.402

Gnomad MID AF: 0.332

Gnomad NFE AF: 0.405

Gnomad OTH AF: 0.330

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

GnomAD4 genome AF: 0.339 AC: 51402 AN: 151850 Hom.: 9261 Cov.: 31 AF XY: 0.337 AC XY: 24972 AN XY: 74188

Gnomad4 AFR AF: 0.225

Gnomad4 AMR AF: 0.389

Gnomad4 ASJ AF: 0.332

Gnomad4 EAS AF: 0.107

Gnomad4 SAS AF: 0.337

Gnomad4 FIN AF: 0.402

Gnomad4 NFE AF: 0.405

Gnomad4 OTH AF: 0.327

Alfa AF: 0.389 Hom.: 5077

Bravo AF: 0.330

Asia WGS AF: 0.242 AC: 844 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	4.9
Dann	Benign	0.61

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: rs17608620; hg19: chr19-56522923;