19-54927572-AAAAC-A

Variant names:

• chr19-54927572-AAAAC-A
• rs104895515
• ENST00000588756.5:c.2981+29_2981+32delGTTT

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_001127255.2(NLRP7):​c.2981+29_2981+32delGTTT 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_001127255.2 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: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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
NLRP7	NM_001127255.2	c.2981+29_2981+32delGTTT		intron_variant	Intron 10 of 10		NP_001120727.1
NLRP7	NM_001405531.1	c.2981+29_2981+32delGTTT		intron_variant	Intron 12 of 12		NP_001392460.1
NLRP7	NM_139176.4	c.2897+29_2897+32delGTTT		intron_variant	Intron 10 of 10		NP_631915.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NLRP7	ENST00000592784.6	c.2981+29_2981+32delGTTT		intron_variant	Intron 10 of 10	1		ENSP00000468706.1

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

GnomAD2 exomes AF: 0.586 AC: 145854 AN: 248942 AF XY: 0.586

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 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 AC: 17132 AN: 33356

Gnomad4 AMR exome AF: 0.638 AC: 28485 AN: 44628

Gnomad4 ASJ exome AF: 0.621 AC: 16179 AN: 26074

Gnomad4 EAS exome AF: 0.719 AC: 28499 AN: 39664

Gnomad4 SAS exome AF: 0.630 AC: 53731 AN: 85344

Gnomad4 FIN exome AF: 0.549 AC: 28936 AN: 52672

Gnomad4 NFE exome AF: 0.545 AC: 604633 AN: 1108930

Gnomad4 Remaining exome AF: 0.572 AC: 34416 AN: 60202

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 AC: 0.521108 AN: 0.521108

Gnomad4 AMR AF: 0.579 AC: 0.57858 AN: 0.57858

Gnomad4 ASJ AF: 0.618 AC: 0.618276 AN: 0.618276

Gnomad4 EAS AF: 0.712 AC: 0.711908 AN: 0.711908

Gnomad4 SAS AF: 0.629 AC: 0.628883 AN: 0.628883

Gnomad4 FIN AF: 0.549 AC: 0.549311 AN: 0.549311

Gnomad4 NFE AF: 0.552 AC: 0.552116 AN: 0.552116

Gnomad4 OTH AF: 0.547 AC: 0.547009 AN: 0.547009

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

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Unité médicale des maladies autoinflammatoires, CHRU Montpellier

Significance: not provided

Review Status: no classification provided

Collection Method: literature only

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
Mutation Taster		=100/0	polymorphism (auto)

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;