19-54927463-G-T

Variant names:

• chr19-54927463-G-T
• rs269931
• NM_001127255.2:c.2981+142C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001127255.2(NLRP7):​c.2981+142C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.552 in 151,166 control chromosomes in the GnomAD database, including 23,187 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as not provided (no stars).

• Frequency:
  • Genomes: 𝑓 0.55 (23187 hom., cov: 30)
  • Exomes 𝑓: 0.57 (99547 hom.)
  • Failed GnomAD Quality Control
• Consequence: NLRP7 NM_001127255.2 intron
• Clinical Significance: not provided no classification provided O:1
• Conservation: PhyloP100: -0.159
• Publications: 2 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.696 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.2981+142C>A		intron	N/A	NP_001120727.1	Q8WX94-3
	NLRP7	NM_001405531.1		c.2981+142C>A		intron	N/A	NP_001392460.1	Q8WX94-3
	NLRP7	NM_139176.4		c.2897+142C>A		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.2981+142C>A		intron	N/A	ENSP00000468706.1	Q8WX94-3
	NLRP7	ENST00000588756.5	TSL:1	c.2981+142C>A		intron	N/A	ENSP00000467123.1	Q8WX94-3
	NLRP7	ENST00000340844.6	TSL:1	c.2810+3036C>A		intron	N/A	ENSP00000339491.2	Q8WX94-1

Frequencies

GnomAD3 genomes AF: 0.552 AC: 83367 AN: 151050 Hom.: 23166 Cov.: 30

Gnomad AFR AF: 0.519

Gnomad AMI AF: 0.283

Gnomad AMR AF: 0.576

Gnomad ASJ AF: 0.607

Gnomad EAS AF: 0.715

Gnomad SAS AF: 0.631

Gnomad FIN AF: 0.548

Gnomad MID AF: 0.571

Gnomad NFE AF: 0.550

Gnomad OTH AF: 0.545

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.574 AC: 343603 AN: 598948 Hom.: 99547 AF XY: 0.578 AC XY: 186365 AN XY: 322502

African (AFR) AF: 0.519 AC: 8137 AN: 15670

American (AMR) AF: 0.634 AC: 19884 AN: 31370

Ashkenazi Jewish (ASJ) AF: 0.612 AC: 11669 AN: 19080

East Asian (EAS) AF: 0.722 AC: 23960 AN: 33204

South Asian (SAS) AF: 0.637 AC: 38387 AN: 60272

European-Finnish (FIN) AF: 0.550 AC: 19290 AN: 35072

Middle Eastern (MID) AF: 0.629 AC: 1825 AN: 2900

European-Non Finnish (NFE) AF: 0.547 AC: 202376 AN: 369654

Other (OTH) AF: 0.570 AC: 18075 AN: 31726

GnomAD4 genome AF: 0.552 AC: 83431 AN: 151166 Hom.: 23187 Cov.: 30 AF XY: 0.555 AC XY: 41017 AN XY: 73862

African (AFR) AF: 0.519 AC: 21374 AN: 41174

American (AMR) AF: 0.576 AC: 8731 AN: 15158

Ashkenazi Jewish (ASJ) AF: 0.607 AC: 2097 AN: 3456

East Asian (EAS) AF: 0.716 AC: 3654 AN: 5106

South Asian (SAS) AF: 0.630 AC: 3026 AN: 4800

European-Finnish (FIN) AF: 0.548 AC: 5716 AN: 10424

Middle Eastern (MID) AF: 0.576 AC: 167 AN: 290

European-Non Finnish (NFE) AF: 0.550 AC: 37272 AN: 67758

Other (OTH) AF: 0.543 AC: 1138 AN: 2096

Alfa AF: 0.421 Hom.: 1075

Bravo AF: 0.554

Asia WGS AF: 0.616 AC: 2145 AN: 3478

ClinVar

ClinVar submissions

Significance: not provided

Revision: no classification provided

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	11
DANN	Benign	0.83
PhyloP100		-0.16
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: rs269931; hg19: chr19-55438831;