19-54927482-A-G

Position:

• chr19-54927482-A-G

Variant summary

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

The NM_001127255.2(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_001127255.2 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:6731): (natural cytotoxicity triggering receptor 1) Predicted to be involved in cellular defense response; regulation of natural killer cell mediated cytotoxicity; and signal transduction. Predicted to act upstream of or within defense response to virus and detection of virus. Predicted to be located in cell surface. Predicted to be part of SWI/SNF complex. Predicted to be active in plasma membrane. Biomarker of acquired immunodeficiency syndrome; anogenital venereal wart; hepatitis C; and lymphoproliferative syndrome. [provided by Alliance of Genome Resources, Apr 2022]

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	Protein	UniProt
NLRP7	NM_001127255.2	c.2981+123T>C		intron_variant			NP_001120727.1
NLRP7	NM_001405531.1	c.2981+123T>C		intron_variant			NP_001392460.1
NLRP7	NM_139176.4	c.2897+123T>C		intron_variant			NP_631915.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NLRP7	ENST00000592784.6	c.2981+123T>C		intron_variant		1		ENSP00000468706.1

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;