rs269949

chr19-54930401-G-A

Variant summary

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

The NM_001405531.1(NLRP7):c.2810+98C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.566 in 812,880 control chromosomes in the GnomAD database, including 132,608 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.55 (23304 hom., cov: 30)
  • Exomes 𝑓: 0.57 (109304 hom.)
• Consequence: NLRP7 NM_001405531.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.30

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=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.695 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NLRP7	NM_001127255.2	c.2810+98C>T		intron_variant		ENST00000592784.6
NLRP7	NM_001405531.1	c.2810+98C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NLRP7	ENST00000592784.6	c.2810+98C>T		intron_variant		1	NM_001127255.2	P2

Frequencies

GnomAD3 genomes AF: 0.553 AC: 83571 AN: 151146 Hom.: 23281 Cov.: 30

Gnomad AFR AF: 0.517

Gnomad AMI AF: 0.287

Gnomad AMR AF: 0.577

Gnomad ASJ AF: 0.627

Gnomad EAS AF: 0.713

Gnomad SAS AF: 0.636

Gnomad FIN AF: 0.551

Gnomad MID AF: 0.565

Gnomad NFE AF: 0.552

Gnomad OTH AF: 0.548

GnomAD4 exome AF: 0.569 AC: 376241 AN: 661614 Hom.: 109304 AF XY: 0.573 AC XY: 202825 AN XY: 353876

Gnomad4 AFR exome AF: 0.514

Gnomad4 AMR exome AF: 0.634

Gnomad4 ASJ exome AF: 0.627

Gnomad4 EAS exome AF: 0.719

Gnomad4 SAS exome AF: 0.637

Gnomad4 FIN exome AF: 0.547

Gnomad4 NFE exome AF: 0.541

Gnomad4 OTH exome AF: 0.569

GnomAD4 genome AF: 0.553 AC: 83638 AN: 151266 Hom.: 23304 Cov.: 30 AF XY: 0.556 AC XY: 41109 AN XY: 73904

Gnomad4 AFR AF: 0.517

Gnomad4 AMR AF: 0.577

Gnomad4 ASJ AF: 0.627

Gnomad4 EAS AF: 0.714

Gnomad4 SAS AF: 0.635

Gnomad4 FIN AF: 0.551

Gnomad4 NFE AF: 0.552

Gnomad4 OTH AF: 0.545

Alfa AF: 0.551 Hom.: 15875

Bravo AF: 0.554

Asia WGS AF: 0.618 AC: 2152 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
Cadd	Benign	0.84
Dann	Benign	0.67

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs269949; hg19: chr19-55441769;