19-56017975-A-T

Position:

• chr19-56017975-A-T

Variant summary

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

The NM_153447.4(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 NM_153447.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.501

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=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.786 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NLRP5	NM_153447.4	c.566-1367A>T		intron_variant		ENST00000390649.8	NP_703148.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NLRP5	ENST00000390649.8	c.566-1367A>T		intron_variant		1	NM_153447.4	ENSP00000375063	P1
NLRP5	ENST00000597673.1	c.485-637A>T		intron_variant, NMD_transcript_variant		5		ENSP00000471494

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

Gnomad4 AFR AF: 0.793

Gnomad4 AMR AF: 0.503

Gnomad4 ASJ AF: 0.489

Gnomad4 EAS AF: 0.549

Gnomad4 SAS AF: 0.512

Gnomad4 FIN AF: 0.523

Gnomad4 NFE AF: 0.480

Gnomad4 OTH AF: 0.565

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 v4.3

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

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: rs306425; hg19: chr19-56529341;