19-54927482-A-G

Variant summary

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

The NM_001405531.1(NLRP7):c.2981+123T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.555 in 150,932 control chromosomes in the GnomAD database, including 23,349 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as not provided (no stars).

• Frequency:
  • Genomes: 𝑓 0.56 (23349 hom., cov: 31)
  • Exomes 𝑓: 0.57 (117499 hom.)
  • Failed GnomAD Quality Control
• Consequence: NLRP7 NM_001405531.1 intron
• Clinical Significance: not provided no classification provided O:1
• Conservation: PhyloP100: -0.146

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.699 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NLRP7	NM_001127255.2	c.2981+123T>C		intron_variant		ENST00000592784.6
NLRP7	NM_001405531.1	c.2981+123T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NLRP7	ENST00000592784.6	c.2981+123T>C		intron_variant		1	NM_001127255.2	P2

Frequencies

GnomAD3 genomes AF: 0.555 AC: 83714 AN: 150816 Hom.: 23328 Cov.: 31

Gnomad AFR AF: 0.522

Gnomad AMI AF: 0.290

Gnomad AMR AF: 0.578

Gnomad ASJ AF: 0.617

Gnomad EAS AF: 0.718

Gnomad SAS AF: 0.635

Gnomad FIN AF: 0.550

Gnomad MID AF: 0.567

Gnomad NFE AF: 0.553

Gnomad OTH AF: 0.548

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.569 AC: 407233 AN: 716218 Hom.: 117499 AF XY: 0.573 AC XY: 218256 AN XY: 380790

Gnomad4 AFR exome AF: 0.517

Gnomad4 AMR exome AF: 0.640

Gnomad4 ASJ exome AF: 0.623

Gnomad4 EAS exome AF: 0.721

Gnomad4 SAS exome AF: 0.638

Gnomad4 FIN exome AF: 0.553

Gnomad4 NFE exome AF: 0.542

Gnomad4 OTH exome AF: 0.570

GnomAD4 genome AF: 0.555 AC: 83778 AN: 150932 Hom.: 23349 Cov.: 31 AF XY: 0.558 AC XY: 41174 AN XY: 73744

Gnomad4 AFR AF: 0.522

Gnomad4 AMR AF: 0.579

Gnomad4 ASJ AF: 0.617

Gnomad4 EAS AF: 0.719

Gnomad4 SAS AF: 0.634

Gnomad4 FIN AF: 0.550

Gnomad4 NFE AF: 0.553

Gnomad4 OTH AF: 0.546

Alfa AF: 0.555 Hom.: 2796

Bravo AF: 0.555

Asia WGS AF: 0.618 AC: 2151 AN: 3478

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

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
Cadd	Benign	5.4
Dann	Benign	0.60

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: rs269932; hg19: chr19-55438850;