19-54923560-C-G

Variant names:

• chr19-54923560-C-G
• rs775865
• NM_001127255.2:c.*180G>C

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.*180G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00754 in 710,168 control chromosomes in the GnomAD database, including 167 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.023 (113 hom., cov: 32)
  • Exomes 𝑓: 0.0034 (54 hom.)
• Consequence: NLRP7 NM_001127255.2 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.513
• Publications: 1 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BP6: Variant 19-54923560-C-G is Benign according to our data. Variant chr19-54923560-C-G is described in ClinVar as Likely_benign. ClinVar VariationId is 330153.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0753 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.*180G>C		3_prime_UTR	Exon 11 of 11	NP_001120727.1	Q8WX94-3
	NLRP7	NM_001405531.1		c.*180G>C		3_prime_UTR	Exon 13 of 13	NP_001392460.1	Q8WX94-3
	NLRP7	NM_139176.4		c.*180G>C		3_prime_UTR	Exon 11 of 11	NP_631915.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NLRP7	ENST00000592784.6	TSL:1 MANE Select	c.*180G>C		3_prime_UTR	Exon 11 of 11	ENSP00000468706.1	Q8WX94-3
	NLRP7	ENST00000588756.5	TSL:1	c.*180G>C		3_prime_UTR	Exon 13 of 13	ENSP00000467123.1	Q8WX94-3
	NLRP7	ENST00000340844.6	TSL:1	c.*180G>C		3_prime_UTR	Exon 10 of 10	ENSP00000339491.2	Q8WX94-1

Frequencies

GnomAD3 genomes AF: 0.0227 AC: 3455 AN: 152136 Hom.: 114 Cov.: 32

Gnomad AFR AF: 0.0776

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0100

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00103

Gnomad FIN AF: 0.0000942

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000691

Gnomad OTH AF: 0.0172

GnomAD4 exome AF: 0.00339 AC: 1893 AN: 557914 Hom.: 54 Cov.: 6 AF XY: 0.00281 AC XY: 844 AN XY: 300454

African (AFR) AF: 0.0808 AC: 1257 AN: 15564

American (AMR) AF: 0.00590 AC: 186 AN: 31502

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17386

East Asian (EAS) AF: 0.00 AC: 0 AN: 33974

South Asian (SAS) AF: 0.000362 AC: 21 AN: 58024

European-Finnish (FIN) AF: 0.0000853 AC: 3 AN: 35158

Middle Eastern (MID) AF: 0.0123 AC: 28 AN: 2282

European-Non Finnish (NFE) AF: 0.000552 AC: 184 AN: 333550

Other (OTH) AF: 0.00702 AC: 214 AN: 30474

GnomAD4 genome AF: 0.0227 AC: 3463 AN: 152254 Hom.: 113 Cov.: 32 AF XY: 0.0216 AC XY: 1609 AN XY: 74448

African (AFR) AF: 0.0775 AC: 3220 AN: 41526

American (AMR) AF: 0.0100 AC: 153 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.000829 AC: 4 AN: 4828

European-Finnish (FIN) AF: 0.0000942 AC: 1 AN: 10620

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.000691 AC: 47 AN: 68016

Other (OTH) AF: 0.0170 AC: 36 AN: 2116

Alfa AF: 0.0174 Hom.: 9

Bravo AF: 0.0267

Asia WGS AF: 0.00433 AC: 15 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Hydatidiform mole, recurrent, 1 (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.4
DANN	Benign	0.41
PhyloP100		-0.51
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: rs775865; hg19: chr19-55434928;