19-54927803-G-A

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_Strong BS1_Supporting BS2

The NM_001405531.1(NLRP7):c.2811-28C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00175 in 1,604,258 control chromosomes in the GnomAD database, including 37 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 0.0085 (21 hom., cov: 33)
  • Exomes 𝑓: 0.0011 (16 hom.)
• Consequence: NLRP7 NM_001405531.1 intron
• Clinical Significance: not provided no classification provided O:1
• Conservation: PhyloP100: -0.659

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 -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00847 (1289/152220) while in subpopulation AFR AF= 0.0281 (1168/41552). AF 95% confidence interval is 0.0268. There are 21 homozygotes in gnomad4. There are 613 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting
• BS2: High Homozygotes in GnomAd at 22 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NLRP7	NM_001127255.2	c.2811-28C>T		intron_variant		ENST00000592784.6
NLRP7	NM_001405531.1	c.2811-28C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NLRP7	ENST00000592784.6	c.2811-28C>T		intron_variant		1	NM_001127255.2	P2

Frequencies

GnomAD3 genomes AF: 0.00845 AC: 1286 AN: 152102 Hom.: 22 Cov.: 33

Gnomad AFR AF: 0.0281

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00577

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000309

Gnomad OTH AF: 0.00576

GnomAD3 exomes AF: 0.00225 AC: 566 AN: 251188 Hom.: 15 AF XY: 0.00162 AC XY: 220 AN XY: 135768

Gnomad AFR exome AF: 0.0299

Gnomad AMR exome AF: 0.00124

Gnomad ASJ exome AF: 0.0000992

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000229

Gnomad OTH exome AF: 0.00147

GnomAD4 exome AF: 0.00105 AC: 1525 AN: 1452038 Hom.: 16 Cov.: 31 AF XY: 0.000927 AC XY: 670 AN XY: 723134

Gnomad4 AFR exome AF: 0.0278

Gnomad4 AMR exome AF: 0.00161

Gnomad4 ASJ exome AF: 0.0000384

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000465

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000333

Gnomad4 OTH exome AF: 0.00242

GnomAD4 genome AF: 0.00847 AC: 1289 AN: 152220 Hom.: 21 Cov.: 33 AF XY: 0.00824 AC XY: 613 AN XY: 74432

Gnomad4 AFR AF: 0.0281

Gnomad4 AMR AF: 0.00576

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000309

Gnomad4 OTH AF: 0.00570

Alfa AF: 0.00692 Hom.: 3

Bravo AF: 0.00925

Asia WGS AF: 0.00173 AC: 6 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	-0.90
Cadd	Benign	4.5
Dann	Benign	0.58

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: rs116109745; hg19: chr19-55439171; COSMIC: COSV60179497;