19-56017975-A-T

Variant names:

• chr19-56017975-A-T
• rs306425
• ENST00000390649.8:c.566-1367A>T

Variant summary

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

The ENST00000390649.8(NLRP5):​c.566-1367A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.576 in 152,012 control chromosomes in the GnomAD database, including 26,717 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 0.58 (26717 hom., cov: 32)
• Consequence: NLRP5 ENST00000390649.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.501
• Publications: 0 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=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.786 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NLRP5	NM_001433705.1		c.413-1367A>T		intron	N/A	NP_001420634.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NLRP5	ENST00000390649.8	TSL:1 MANE Select	c.566-1367A>T		intron	N/A	ENSP00000375063.3	P59047
	NLRP5	ENST00000850973.1		c.413-1367A>T		intron	N/A	ENSP00000521055.1
	NLRP5	ENST00000597673.1	TSL:5	n.485-637A>T		intron	N/A	ENSP00000471494.1	M0R0W4

Frequencies

GnomAD3 genomes AF: 0.576 AC: 87435 AN: 151894 Hom.: 26671 Cov.: 32

Gnomad AFR AF: 0.793

Gnomad AMI AF: 0.576

Gnomad AMR AF: 0.503

Gnomad ASJ AF: 0.489

Gnomad EAS AF: 0.549

Gnomad SAS AF: 0.512

Gnomad FIN AF: 0.523

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.480

Gnomad OTH AF: 0.566

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

GnomAD4 genome AF: 0.576 AC: 87547 AN: 152012 Hom.: 26717 Cov.: 32 AF XY: 0.575 AC XY: 42700 AN XY: 74282

African (AFR) AF: 0.793 AC: 32893 AN: 41466

American (AMR) AF: 0.503 AC: 7678 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.489 AC: 1693 AN: 3464

East Asian (EAS) AF: 0.549 AC: 2841 AN: 5172

South Asian (SAS) AF: 0.512 AC: 2464 AN: 4814

European-Finnish (FIN) AF: 0.523 AC: 5517 AN: 10548

Middle Eastern (MID) AF: 0.500 AC: 147 AN: 294

European-Non Finnish (NFE) AF: 0.480 AC: 32599 AN: 67978

Other (OTH) AF: 0.565 AC: 1192 AN: 2110

Alfa AF: 0.538 Hom.: 3183

Bravo AF: 0.583

Asia WGS AF: 0.546 AC: 1903 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.2
DANN	Benign	0.46
PhyloP100		-0.50
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs306425;

hg19: chr19-56529341;