19-55989684-A-G

Variant names:

• chr19-55989684-A-G
• rs306450
• NM_001433705.1:c.-72+2863A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001433705.1(NLRP5):​c.-72+2863A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.417 in 152,012 control chromosomes in the GnomAD database, including 13,468 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 0.42 (13468 hom., cov: 33)
• Consequence: NLRP5 NM_001433705.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.54
• Publications: 11 publications found

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]

NLRP5 Gene-Disease associations (from GenCC):

• oocyte/zygote/embryo maturation arrest 19

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.524 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NLRP5	NM_001433705.1	c.-72+2863A>G		intron_variant	Intron 1 of 14		NP_001420634.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD3 genomes AF: 0.417 AC: 63284 AN: 151892 Hom.: 13461 Cov.: 33

Gnomad AFR AF: 0.476

Gnomad AMI AF: 0.432

Gnomad AMR AF: 0.372

Gnomad ASJ AF: 0.463

Gnomad EAS AF: 0.541

Gnomad SAS AF: 0.399

Gnomad FIN AF: 0.267

Gnomad MID AF: 0.462

Gnomad NFE AF: 0.402

Gnomad OTH AF: 0.424

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

GnomAD4 genome AF: 0.417 AC: 63340 AN: 152012 Hom.: 13468 Cov.: 33 AF XY: 0.410 AC XY: 30441 AN XY: 74308

African (AFR) AF: 0.476 AC: 19747 AN: 41468

American (AMR) AF: 0.372 AC: 5672 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.463 AC: 1608 AN: 3472

East Asian (EAS) AF: 0.541 AC: 2792 AN: 5164

South Asian (SAS) AF: 0.400 AC: 1925 AN: 4814

European-Finnish (FIN) AF: 0.267 AC: 2816 AN: 10550

Middle Eastern (MID) AF: 0.463 AC: 136 AN: 294

European-Non Finnish (NFE) AF: 0.402 AC: 27351 AN: 67964

Other (OTH) AF: 0.426 AC: 900 AN: 2112

Alfa AF: 0.413 Hom.: 36264

Bravo AF: 0.430

Asia WGS AF: 0.488 AC: 1694 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	0.25
DANN	Benign	0.26
PhyloP100		-1.5

Splicing

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

Other links and lift over

dbSNP: rs306450; hg19: chr19-56501050;