19-54927798-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001405531.1(NLRP7):c.2811-23A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.56 in 1,605,672 control chromosomes in the GnomAD database, including 254,459 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.56 (23702 hom., cov: 32)
  • Exomes 𝑓: 0.56 (230757 hom.)
• Consequence: NLRP7 NM_001405531.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.672

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BP6: Variant 19-54927798-T-C is Benign according to our data. Variant chr19-54927798-T-C is described in ClinVar as [Benign]. Clinvar id is 997711.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.697 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NLRP7	NM_001127255.2	c.2811-23A>G		intron_variant		ENST00000592784.6
NLRP7	NM_001405531.1	c.2811-23A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NLRP7	ENST00000592784.6	c.2811-23A>G		intron_variant		1	NM_001127255.2	P2

Frequencies

GnomAD3 genomes AF: 0.555 AC: 84369 AN: 151888 Hom.: 23681 Cov.: 32

Gnomad AFR AF: 0.523

Gnomad AMI AF: 0.287

Gnomad AMR AF: 0.578

Gnomad ASJ AF: 0.619

Gnomad EAS AF: 0.715

Gnomad SAS AF: 0.634

Gnomad FIN AF: 0.552

Gnomad MID AF: 0.573

Gnomad NFE AF: 0.553

Gnomad OTH AF: 0.549

GnomAD3 exomes AF: 0.587 AC: 147604 AN: 251264 Hom.: 44016 AF XY: 0.589 AC XY: 79938 AN XY: 135824

Gnomad AFR exome AF: 0.524

Gnomad AMR exome AF: 0.645

Gnomad ASJ exome AF: 0.621

Gnomad EAS exome AF: 0.715

Gnomad SAS exome AF: 0.628

Gnomad FIN exome AF: 0.552

Gnomad NFE exome AF: 0.553

Gnomad OTH exome AF: 0.564

GnomAD4 exome AF: 0.561 AC: 815427 AN: 1453668 Hom.: 230757 Cov.: 33 AF XY: 0.564 AC XY: 408352 AN XY: 723556

Gnomad4 AFR exome AF: 0.515

Gnomad4 AMR exome AF: 0.639

Gnomad4 ASJ exome AF: 0.621

Gnomad4 EAS exome AF: 0.719

Gnomad4 SAS exome AF: 0.635

Gnomad4 FIN exome AF: 0.550

Gnomad4 NFE exome AF: 0.546

Gnomad4 OTH exome AF: 0.573

GnomAD4 genome AF: 0.555 AC: 84433 AN: 152004 Hom.: 23702 Cov.: 32 AF XY: 0.559 AC XY: 41515 AN XY: 74304

Gnomad4 AFR AF: 0.523

Gnomad4 AMR AF: 0.579

Gnomad4 ASJ AF: 0.619

Gnomad4 EAS AF: 0.717

Gnomad4 SAS AF: 0.634

Gnomad4 FIN AF: 0.552

Gnomad4 NFE AF: 0.553

Gnomad4 OTH AF: 0.547

Alfa AF: 0.565 Hom.: 4908

Bravo AF: 0.555

Asia WGS AF: 0.618 AC: 2152 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Hydatidiform mole Benign:1

Benign, criteria provided, single submitter

research

National Health Laboratory Service, Universitas Academic Hospital and University of the Free State

Feb 22, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
Cadd	Benign	0.32
Dann	Benign	0.56

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.13		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: rs269933; hg19: chr19-55439166; COSMIC: COSV60172217;