19-54927798-T-C

Variant names:

• chr19-54927798-T-C
• rs269933
• ENST00000588756.5:c.2811-23A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001127255.2(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_001127255.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• 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: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 -20 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_multiple_submitters_no_conflicts, 2 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 rank	MANE	Protein	UniProt
NLRP7	NM_001127255.2	c.2811-23A>G		intron_variant	Intron 9 of 10		NP_001120727.1
NLRP7	NM_001405531.1	c.2811-23A>G		intron_variant	Intron 11 of 12		NP_001392460.1
NLRP7	NM_139176.4	c.2727-23A>G		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.2811-23A>G		intron_variant	Intron 9 of 10	1		ENSP00000468706.1

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

GnomAD2 exomes AF: 0.587 AC: 147604 AN: 251264 AF XY: 0.589

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 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 AC: 17130 AN: 33284

Gnomad4 AMR exome AF: 0.639 AC: 28580 AN: 44716

Gnomad4 ASJ exome AF: 0.621 AC: 16193 AN: 26078

Gnomad4 EAS exome AF: 0.719 AC: 28494 AN: 39650

Gnomad4 SAS exome AF: 0.635 AC: 54703 AN: 86080

Gnomad4 FIN exome AF: 0.550 AC: 29298 AN: 53316

Gnomad4 NFE exome AF: 0.546 AC: 603079 AN: 1104714

Gnomad4 Remaining exome AF: 0.573 AC: 34416 AN: 60102

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 AC: 0.522777 AN: 0.522777

Gnomad4 AMR AF: 0.579 AC: 0.578906 AN: 0.578906

Gnomad4 ASJ AF: 0.619 AC: 0.61924 AN: 0.61924

Gnomad4 EAS AF: 0.717 AC: 0.716551 AN: 0.716551

Gnomad4 SAS AF: 0.634 AC: 0.633817 AN: 0.633817

Gnomad4 FIN AF: 0.552 AC: 0.551998 AN: 0.551998

Gnomad4 NFE AF: 0.553 AC: 0.553373 AN: 0.553373

Gnomad4 OTH AF: 0.547 AC: 0.546875 AN: 0.546875

Alfa AF: 0.569 Hom.: 9213

Bravo AF: 0.555

Asia WGS AF: 0.618 AC: 2152 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Hydatidiform mole Benign:1

Feb 22, 2021

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

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: research

- -

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.32
DANN	Benign	0.56
Mutation Taster		=100/0	polymorphism (auto)

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;