19-56051999-A-G

Variant names:

• chr19-56051999-A-G
• rs1654394
• ENST00000390649.8:c.3128+1411A>G

Variant summary

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

The ENST00000390649.8(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 ENST00000390649.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.570
• Publications: 1 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=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.206 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000390649.8. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NLRP5	NM_001433705.1		c.2975+1411A>G		intron	N/A	NP_001420634.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NLRP5	ENST00000390649.8	TSL:1 MANE Select	c.3128+1411A>G		intron	N/A	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

African (AFR) AF: 0.107 AC: 4434 AN: 41518

American (AMR) AF: 0.133 AC: 2025 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.198 AC: 688 AN: 3472

East Asian (EAS) AF: 0.0219 AC: 113 AN: 5170

South Asian (SAS) AF: 0.127 AC: 612 AN: 4824

European-Finnish (FIN) AF: 0.155 AC: 1643 AN: 10592

Middle Eastern (MID) AF: 0.224 AC: 66 AN: 294

European-Non Finnish (NFE) AF: 0.209 AC: 14201 AN: 67996

Other (OTH) AF: 0.180 AC: 379 AN: 2108

Alfa AF: 0.191 Hom.: 1724

Bravo AF: 0.156

Asia WGS AF: 0.0660 AC: 231 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	4.7
DANN	Benign	0.76
PhyloP100		0.57
Mutation Taster		=100/0	polymorphism (auto)

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: rs1654394; hg19: chr19-56563365;