rs269949

Variant names:

• chr19-54930401-G-A
• rs269949
• ENST00000588756.5:c.2810+98C>T

Variant summary

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

The NM_001127255.2(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_001127255.2 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: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=-0.79).
• 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 rank	MANE	Protein	UniProt
NLRP7	NM_001127255.2	c.2810+98C>T		intron_variant	Intron 9 of 10		NP_001120727.1
NLRP7	NM_001405531.1	c.2810+98C>T		intron_variant	Intron 11 of 12		NP_001392460.1
NLRP7	NM_139176.4	c.2726+98C>T		intron_variant	Intron 9 of 10		NP_631915.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NLRP7	ENST00000592784.6	c.2810+98C>T		intron_variant	Intron 9 of 10	1		ENSP00000468706.1

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;