19-54927572-AAAAC-A

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_001405531.1(NLRP7):c.2981+29_2981+32del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.559 in 1,607,956 control chromosomes in the GnomAD database, including 253,779 homozygotes. Variant has been reported in ClinVar as not provided (no stars).

• Frequency:
  • Genomes: 𝑓 0.55 (23404 hom., cov: 0)
  • Exomes 𝑓: 0.56 (230375 hom.)
• Consequence: NLRP7 NM_001405531.1 intron
• Clinical Significance: not provided no classification provided O:1
• Conservation: PhyloP100: 0.260

Genes affected

NLRP7 (HGNC:22947): (NLR family pyrin domain containing 7) This gene encodes a member of the NACHT, leucine rich repeat, and PYD containing (NLRP) protein family. It has an N-terminal pyrin domain, followed by a NACHT domain, a NACHT-associated domain (NAD), and a C-terminal leucine-rich repeat (LRR) region. NLRP proteins are implicated in the activation of proinflammatory caspases through multiprotein complexes called inflammasomes. This gene may act as a feedback regulator of caspase-1-dependent interleukin 1-beta secretion. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]

NCR1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.693 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NLRP7	NM_001127255.2	c.2981+29_2981+32del		intron_variant		ENST00000592784.6
NLRP7	NM_001405531.1	c.2981+29_2981+32del		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NLRP7	ENST00000592784.6	c.2981+29_2981+32del		intron_variant		1	NM_001127255.2	P2

Frequencies

GnomAD3 genomes AF: 0.554 AC: 83739 AN: 151210 Hom.: 23382 Cov.: 0

Gnomad AFR AF: 0.521

Gnomad AMI AF: 0.281

Gnomad AMR AF: 0.578

Gnomad ASJ AF: 0.618

Gnomad EAS AF: 0.711

Gnomad SAS AF: 0.629

Gnomad FIN AF: 0.549

Gnomad MID AF: 0.567

Gnomad NFE AF: 0.552

Gnomad OTH AF: 0.549

GnomAD3 exomes AF: 0.586 AC: 145854 AN: 248942 Hom.: 43313 AF XY: 0.586 AC XY: 79109 AN XY: 134930

Gnomad AFR exome AF: 0.523

Gnomad AMR exome AF: 0.644

Gnomad ASJ exome AF: 0.620

Gnomad EAS exome AF: 0.714

Gnomad SAS exome AF: 0.617

Gnomad FIN exome AF: 0.553

Gnomad NFE exome AF: 0.552

Gnomad OTH exome AF: 0.562

GnomAD4 exome AF: 0.560 AC: 815566 AN: 1456626 Hom.: 230375 AF XY: 0.563 AC XY: 408197 AN XY: 724760

Gnomad4 AFR exome AF: 0.514

Gnomad4 AMR exome AF: 0.638

Gnomad4 ASJ exome AF: 0.621

Gnomad4 EAS exome AF: 0.719

Gnomad4 SAS exome AF: 0.630

Gnomad4 FIN exome AF: 0.549

Gnomad4 NFE exome AF: 0.545

Gnomad4 OTH exome AF: 0.572

GnomAD4 genome AF: 0.554 AC: 83805 AN: 151330 Hom.: 23404 Cov.: 0 AF XY: 0.557 AC XY: 41140 AN XY: 73880

Gnomad4 AFR AF: 0.521

Gnomad4 AMR AF: 0.579

Gnomad4 ASJ AF: 0.618

Gnomad4 EAS AF: 0.712

Gnomad4 SAS AF: 0.629

Gnomad4 FIN AF: 0.549

Gnomad4 NFE AF: 0.552

Gnomad4 OTH AF: 0.547

Alfa AF: 0.528 Hom.: 2072

ClinVar

Significance: not provided

Submissions summary: Other:1

Revision: no classification provided

Submissions by phenotype

Hydatidiform mole, recurrent, 1 Other:1

not provided, no classification provided

literature only

Unité médicale des maladies autoinflammatoires, CHRU Montpellier

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Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs104895515; hg19: chr19-55438940;