19-54923899-TCC-TC

Variant names:

• chr19-54923899-TC-T
• rs34438464
• NM_001127255.2:c.2982-28delG

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001127255.2(NLRP7):​c.2982-28delG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0908 in 1,611,612 control chromosomes in the GnomAD database, including 9,093 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.12 (1363 hom., cov: 30)
  • Exomes 𝑓: 0.088 (7730 hom.)
• Consequence: NLRP7 NM_001127255.2 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.799
• Publications: 3 publications found

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 -10 ACMG points.

• BP6: Variant 19-54923899-TC-T is Benign according to our data. Variant chr19-54923899-TC-T is described in ClinVar as Likely_benign. ClinVar VariationId is 997712.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.305 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001127255.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NLRP7	NM_001127255.2	MANE Select	c.2982-28delG		intron	N/A	NP_001120727.1	Q8WX94-3
	NLRP7	NM_001405531.1		c.2982-28delG		intron	N/A	NP_001392460.1	Q8WX94-3
	NLRP7	NM_139176.4		c.2898-28delG		intron	N/A	NP_631915.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NLRP7	ENST00000592784.6	TSL:1 MANE Select	c.2982-28delG		intron	N/A	ENSP00000468706.1	Q8WX94-3
	NLRP7	ENST00000588756.5	TSL:1	c.2982-28delG		intron	N/A	ENSP00000467123.1	Q8WX94-3
	NLRP7	ENST00000340844.6	TSL:1	c.2811-28delG		intron	N/A	ENSP00000339491.2	Q8WX94-1

Frequencies

GnomAD3 genomes AF: 0.118 AC: 17997 AN: 152030 Hom.: 1356 Cov.: 30

Gnomad AFR AF: 0.146

Gnomad AMI AF: 0.0504

Gnomad AMR AF: 0.158

Gnomad ASJ AF: 0.0403

Gnomad EAS AF: 0.317

Gnomad SAS AF: 0.0592

Gnomad FIN AF: 0.194

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0753

Gnomad OTH AF: 0.122

GnomAD2 exomes AF: 0.123 AC: 30541 AN: 248580 AF XY: 0.113

Gnomad AFR exome AF: 0.151

Gnomad AMR exome AF: 0.212

Gnomad ASJ exome AF: 0.0382

Gnomad EAS exome AF: 0.310

Gnomad FIN exome AF: 0.187

Gnomad NFE exome AF: 0.0769

Gnomad OTH exome AF: 0.105

GnomAD4 exome AF: 0.0879 AC: 128243 AN: 1459464 Hom.: 7730 Cov.: 28 AF XY: 0.0855 AC XY: 62092 AN XY: 726178

African (AFR) AF: 0.146 AC: 4875 AN: 33422

American (AMR) AF: 0.209 AC: 9365 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.0384 AC: 1004 AN: 26132

East Asian (EAS) AF: 0.301 AC: 11934 AN: 39674

South Asian (SAS) AF: 0.0472 AC: 4071 AN: 86210

European-Finnish (FIN) AF: 0.180 AC: 9539 AN: 53060

Middle Eastern (MID) AF: 0.0468 AC: 270 AN: 5766

European-Non Finnish (NFE) AF: 0.0733 AC: 81411 AN: 1110156

Other (OTH) AF: 0.0957 AC: 5774 AN: 60328

GnomAD4 genome AF: 0.119 AC: 18038 AN: 152148 Hom.: 1363 Cov.: 30 AF XY: 0.124 AC XY: 9224 AN XY: 74392

African (AFR) AF: 0.146 AC: 6060 AN: 41532

American (AMR) AF: 0.159 AC: 2420 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.0403 AC: 140 AN: 3472

East Asian (EAS) AF: 0.318 AC: 1639 AN: 5156

South Asian (SAS) AF: 0.0589 AC: 284 AN: 4824

European-Finnish (FIN) AF: 0.194 AC: 2053 AN: 10588

Middle Eastern (MID) AF: 0.0374 AC: 11 AN: 294

European-Non Finnish (NFE) AF: 0.0753 AC: 5123 AN: 68006

Other (OTH) AF: 0.124 AC: 262 AN: 2112

Alfa AF: 0.0851 Hom.: 106

Bravo AF: 0.121

Asia WGS AF: 0.192 AC: 670 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Hydatidiform mole (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.80
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs34438464; hg19: chr19-55435267; COSMIC: COSV107398241;