19-54923899-TC-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001405531.1(NLRP7):c.2982-28del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0908 in 1,611,612 control chromosomes in the GnomAD database, including 9,093 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.12 (1363 hom., cov: 30)
  • Exomes 𝑓: 0.088 (7730 hom.)
• Consequence: NLRP7 NM_001405531.1 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.799

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 -10 ACMG points.

• BP6: Variant 19-54923899-TC-T is Benign according to our data. Variant chr19-54923899-TC-T is described in ClinVar as [Likely_benign]. Clinvar id is 997712.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.305 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NLRP7	NM_001127255.2	c.2982-28del		intron_variant		ENST00000592784.6
NLRP7	NM_001405531.1	c.2982-28del		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NLRP7	ENST00000592784.6	c.2982-28del		intron_variant		1	NM_001127255.2	P2

Frequencies

GnomAD3 genomes AF: 0.118 AC: 17997 AN: 152030 Hom.: 1356 Cov.: 30

Gnomad AFR AF: 0.146

Gnomad AMI AF: 0.0504

Gnomad AMR AF: 0.158

Gnomad ASJ AF: 0.0403

Gnomad EAS AF: 0.317

Gnomad SAS AF: 0.0592

Gnomad FIN AF: 0.194

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0753

Gnomad OTH AF: 0.122

GnomAD3 exomes AF: 0.123 AC: 30541 AN: 248580 Hom.: 2725 AF XY: 0.113 AC XY: 15213 AN XY: 134680

Gnomad AFR exome AF: 0.151

Gnomad AMR exome AF: 0.212

Gnomad ASJ exome AF: 0.0382

Gnomad EAS exome AF: 0.310

Gnomad SAS exome AF: 0.0486

Gnomad FIN exome AF: 0.187

Gnomad NFE exome AF: 0.0769

Gnomad OTH exome AF: 0.105

GnomAD4 exome AF: 0.0879 AC: 128243 AN: 1459464 Hom.: 7730 Cov.: 28 AF XY: 0.0855 AC XY: 62092 AN XY: 726178

Gnomad4 AFR exome AF: 0.146

Gnomad4 AMR exome AF: 0.209

Gnomad4 ASJ exome AF: 0.0384

Gnomad4 EAS exome AF: 0.301

Gnomad4 SAS exome AF: 0.0472

Gnomad4 FIN exome AF: 0.180

Gnomad4 NFE exome AF: 0.0733

Gnomad4 OTH exome AF: 0.0957

GnomAD4 genome AF: 0.119 AC: 18038 AN: 152148 Hom.: 1363 Cov.: 30 AF XY: 0.124 AC XY: 9224 AN XY: 74392

Gnomad4 AFR AF: 0.146

Gnomad4 AMR AF: 0.159

Gnomad4 ASJ AF: 0.0403

Gnomad4 EAS AF: 0.318

Gnomad4 SAS AF: 0.0589

Gnomad4 FIN AF: 0.194

Gnomad4 NFE AF: 0.0753

Gnomad4 OTH AF: 0.124

Alfa AF: 0.0851 Hom.: 106

Bravo AF: 0.121

Asia WGS AF: 0.192 AC: 670 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Hydatidiform mole Benign:1

Likely benign, criteria provided, single submitter

research

National Health Laboratory Service, Universitas Academic Hospital and University of the Free State

Feb 22, 2021

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Computational scores

Source: dbNSFP v4.3

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: rs34438464; hg19: chr19-55435267;