rs1654394

Positions:

• chr19-56051999-A-G

Variant summary

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

The NM_153447.4(NLRP5):​c.3128+1411A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.161 in 152,162 control chromosomes in the GnomAD database, including 2,245 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 0.16 (2245 hom., cov: 32)
• Consequence: NLRP5 NM_153447.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.570

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=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.206 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NLRP5	NM_153447.4	c.3128+1411A>G		intron_variant		ENST00000390649.8	NP_703148.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NLRP5	ENST00000390649.8	c.3128+1411A>G		intron_variant		1	NM_153447.4	ENSP00000375063.3

Frequencies

GnomAD3 genomes AF: 0.161 AC: 24534 AN: 152044 Hom.: 2242 Cov.: 32

Gnomad AFR AF: 0.106

Gnomad AMI AF: 0.443

Gnomad AMR AF: 0.133

Gnomad ASJ AF: 0.198

Gnomad EAS AF: 0.0216

Gnomad SAS AF: 0.127

Gnomad FIN AF: 0.155

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.209

Gnomad OTH AF: 0.182

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

GnomAD4 genome AF: 0.161 AC: 24564 AN: 152162 Hom.: 2245 Cov.: 32 AF XY: 0.158 AC XY: 11727 AN XY: 74380

Gnomad4 AFR AF: 0.107

Gnomad4 AMR AF: 0.133

Gnomad4 ASJ AF: 0.198

Gnomad4 EAS AF: 0.0219

Gnomad4 SAS AF: 0.127

Gnomad4 FIN AF: 0.155

Gnomad4 NFE AF: 0.209

Gnomad4 OTH AF: 0.180

Alfa AF: 0.191 Hom.: 1559

Bravo AF: 0.156

Asia WGS AF: 0.0660 AC: 231 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	4.7
DANN	Benign	0.76

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: rs1654394; hg19: chr19-56563365;