19-54939682-C-T

Variant names:

• chr19-54939682-C-T
• rs10418277
• NM_001127255.2:c.1137G>A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001127255.2(NLRP7):​c.1137G>A​(p.Lys379Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.211 in 1,612,666 control chromosomes in the GnomAD database, including 36,759 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.19 (2952 hom., cov: 31)
  • Exomes 𝑓: 0.21 (33807 hom.)
• Consequence: NLRP7 NM_001127255.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -6.88
• Publications: 16 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]

NLRP7 Gene-Disease associations (from GenCC):

• hydatidiform mole, recurrent, 1

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• complete hydatidiform mole

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 19-54939682-C-T is Benign according to our data. Variant chr19-54939682-C-T is described in ClinVar as Benign. ClinVar VariationId is 330172.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-6.88 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.266 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.1137G>A	p.Lys379Lys	synonymous	Exon 4 of 11	NP_001120727.1	Q8WX94-3
	NLRP7	NM_001405531.1		c.1137G>A	p.Lys379Lys	synonymous	Exon 6 of 13	NP_001392460.1	Q8WX94-3
	NLRP7	NM_139176.4		c.1137G>A	p.Lys379Lys	synonymous	Exon 4 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.1137G>A	p.Lys379Lys	synonymous	Exon 4 of 11	ENSP00000468706.1	Q8WX94-3
	NLRP7	ENST00000588756.5	TSL:1	c.1137G>A	p.Lys379Lys	synonymous	Exon 6 of 13	ENSP00000467123.1	Q8WX94-3
	NLRP7	ENST00000340844.6	TSL:1	c.1137G>A	p.Lys379Lys	synonymous	Exon 4 of 10	ENSP00000339491.2	Q8WX94-1

Frequencies

GnomAD3 genomes AF: 0.189 AC: 28674 AN: 151800 Hom.: 2948 Cov.: 31

Gnomad AFR AF: 0.116

Gnomad AMI AF: 0.239

Gnomad AMR AF: 0.273

Gnomad ASJ AF: 0.201

Gnomad EAS AF: 0.167

Gnomad SAS AF: 0.219

Gnomad FIN AF: 0.210

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.208

Gnomad OTH AF: 0.202

GnomAD2 exomes AF: 0.212 AC: 52890 AN: 249060 AF XY: 0.211

Gnomad AFR exome AF: 0.114

Gnomad AMR exome AF: 0.302

Gnomad ASJ exome AF: 0.212

Gnomad EAS exome AF: 0.146

Gnomad FIN exome AF: 0.213

Gnomad NFE exome AF: 0.207

Gnomad OTH exome AF: 0.227

GnomAD4 exome AF: 0.213 AC: 311722 AN: 1460750 Hom.: 33807 Cov.: 74 AF XY: 0.213 AC XY: 154719 AN XY: 726708

African (AFR) AF: 0.116 AC: 3881 AN: 33444

American (AMR) AF: 0.294 AC: 13126 AN: 44676

Ashkenazi Jewish (ASJ) AF: 0.214 AC: 5579 AN: 26130

East Asian (EAS) AF: 0.172 AC: 6821 AN: 39698

South Asian (SAS) AF: 0.224 AC: 19307 AN: 86206

European-Finnish (FIN) AF: 0.213 AC: 11339 AN: 53212

Middle Eastern (MID) AF: 0.208 AC: 1072 AN: 5164

European-Non Finnish (NFE) AF: 0.214 AC: 238192 AN: 1111904

Other (OTH) AF: 0.206 AC: 12405 AN: 60316

GnomAD4 genome AF: 0.189 AC: 28688 AN: 151916 Hom.: 2952 Cov.: 31 AF XY: 0.191 AC XY: 14213 AN XY: 74254

African (AFR) AF: 0.116 AC: 4825 AN: 41468

American (AMR) AF: 0.273 AC: 4161 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.201 AC: 699 AN: 3470

East Asian (EAS) AF: 0.168 AC: 859 AN: 5120

South Asian (SAS) AF: 0.219 AC: 1052 AN: 4798

European-Finnish (FIN) AF: 0.210 AC: 2225 AN: 10596

Middle Eastern (MID) AF: 0.238 AC: 70 AN: 294

European-Non Finnish (NFE) AF: 0.208 AC: 14158 AN: 67912

Other (OTH) AF: 0.201 AC: 422 AN: 2102

Alfa AF: 0.127 Hom.: 426

Bravo AF: 0.189

EpiCase AF: 0.208

EpiControl AF: 0.211

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.33
DANN	Benign	0.47
PhyloP100		-6.9
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: rs10418277; hg19: chr19-55451050; COSMIC: COSV60174398; COSMIC: COSV60174398;