rs775883

Variant names:

• chr19-54940429-C-T
• rs775883
• NM_001127255.2:c.390G>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.390G>A​(p.Gln130Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.347 in 1,613,056 control chromosomes in the GnomAD database, including 99,682 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.39 (12081 hom., cov: 32)
  • Exomes 𝑓: 0.34 (87601 hom.)
• Consequence: NLRP7 NM_001127255.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -2.74
• Publications: 23 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=-1.01).
• BP6: Variant 19-54940429-C-T is Benign according to our data. Variant chr19-54940429-C-T is described in ClinVar as Benign. ClinVar VariationId is 330183.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-2.74 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.498 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.390G>A	p.Gln130Gln	synonymous	Exon 4 of 11	NP_001120727.1	Q8WX94-3
	NLRP7	NM_001405531.1		c.390G>A	p.Gln130Gln	synonymous	Exon 6 of 13	NP_001392460.1	Q8WX94-3
	NLRP7	NM_139176.4		c.390G>A	p.Gln130Gln	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.390G>A	p.Gln130Gln	synonymous	Exon 4 of 11	ENSP00000468706.1	Q8WX94-3
	NLRP7	ENST00000588756.5	TSL:1	c.390G>A	p.Gln130Gln	synonymous	Exon 6 of 13	ENSP00000467123.1	Q8WX94-3
	NLRP7	ENST00000340844.6	TSL:1	c.390G>A	p.Gln130Gln	synonymous	Exon 4 of 10	ENSP00000339491.2	Q8WX94-1

Frequencies

GnomAD3 genomes AF: 0.388 AC: 58899 AN: 151894 Hom.: 12050 Cov.: 32

Gnomad AFR AF: 0.503

Gnomad AMI AF: 0.401

Gnomad AMR AF: 0.400

Gnomad ASJ AF: 0.352

Gnomad EAS AF: 0.179

Gnomad SAS AF: 0.261

Gnomad FIN AF: 0.391

Gnomad MID AF: 0.411

Gnomad NFE AF: 0.341

Gnomad OTH AF: 0.383

GnomAD2 exomes AF: 0.341 AC: 85406 AN: 250632 AF XY: 0.333

Gnomad AFR exome AF: 0.508

Gnomad AMR exome AF: 0.383

Gnomad ASJ exome AF: 0.356

Gnomad EAS exome AF: 0.153

Gnomad FIN exome AF: 0.399

Gnomad NFE exome AF: 0.342

Gnomad OTH exome AF: 0.364

GnomAD4 exome AF: 0.342 AC: 500020 AN: 1461044 Hom.: 87601 Cov.: 37 AF XY: 0.339 AC XY: 246746 AN XY: 726892

African (AFR) AF: 0.511 AC: 17115 AN: 33464

American (AMR) AF: 0.380 AC: 17000 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.358 AC: 9345 AN: 26130

East Asian (EAS) AF: 0.189 AC: 7489 AN: 39696

South Asian (SAS) AF: 0.267 AC: 23068 AN: 86246

European-Finnish (FIN) AF: 0.395 AC: 21067 AN: 53382

Middle Eastern (MID) AF: 0.364 AC: 2100 AN: 5768

European-Non Finnish (NFE) AF: 0.344 AC: 381927 AN: 1111266

Other (OTH) AF: 0.346 AC: 20909 AN: 60370

GnomAD4 genome AF: 0.388 AC: 58985 AN: 152012 Hom.: 12081 Cov.: 32 AF XY: 0.388 AC XY: 28820 AN XY: 74300

African (AFR) AF: 0.504 AC: 20900 AN: 41480

American (AMR) AF: 0.399 AC: 6088 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.352 AC: 1220 AN: 3468

East Asian (EAS) AF: 0.179 AC: 926 AN: 5166

South Asian (SAS) AF: 0.261 AC: 1258 AN: 4826

European-Finnish (FIN) AF: 0.391 AC: 4136 AN: 10570

Middle Eastern (MID) AF: 0.412 AC: 121 AN: 294

European-Non Finnish (NFE) AF: 0.341 AC: 23163 AN: 67942

Other (OTH) AF: 0.382 AC: 807 AN: 2110

Alfa AF: 0.359 Hom.: 32130

Bravo AF: 0.394

Asia WGS AF: 0.288 AC: 1004 AN: 3478

EpiCase AF: 0.335

EpiControl AF: 0.345

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	Hydatidiform mole, recurrent, 1 (3)
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.13
DANN	Benign	0.21
PhyloP100		-2.7
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs775883; hg19: chr19-55451797; COSMIC: COSV60172253; COSMIC: COSV60172253;