rs269951

Variant names:

• chr19-54930627-A-G
• rs269951
• NM_001127255.2:c.2682T>C

Your query was ambiguous. Multiple possible variants found:

• chr19-54930627-A-G
• chr19-54930627-A-T

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.2682T>C​(p.Tyr894Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.561 in 1,610,306 control chromosomes in the GnomAD database, including 255,126 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.55 (23580 hom., cov: 31)
  • Exomes 𝑓: 0.56 (231546 hom.)
• Consequence: NLRP7 NM_001127255.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -0.264
• Publications: 22 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=-1.03).
• BP6: Variant 19-54930627-A-G is Benign according to our data. Variant chr19-54930627-A-G is described in ClinVar as Benign. ClinVar VariationId is 330158.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.698 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.2682T>C	p.Tyr894Tyr	synonymous	Exon 9 of 11	NP_001120727.1	Q8WX94-3
	NLRP7	NM_001405531.1		c.2682T>C	p.Tyr894Tyr	synonymous	Exon 11 of 13	NP_001392460.1	Q8WX94-3
	NLRP7	NM_139176.4		c.2598T>C	p.Tyr866Tyr	synonymous	Exon 9 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.2682T>C	p.Tyr894Tyr	synonymous	Exon 9 of 11	ENSP00000468706.1	Q8WX94-3
	NLRP7	ENST00000588756.5	TSL:1	c.2682T>C	p.Tyr894Tyr	synonymous	Exon 11 of 13	ENSP00000467123.1	Q8WX94-3
	NLRP7	ENST00000340844.6	TSL:1	c.2682T>C	p.Tyr894Tyr	synonymous	Exon 9 of 10	ENSP00000339491.2	Q8WX94-1

Frequencies

GnomAD3 genomes AF: 0.554 AC: 84139 AN: 151824 Hom.: 23559 Cov.: 31

Gnomad AFR AF: 0.518

Gnomad AMI AF: 0.288

Gnomad AMR AF: 0.577

Gnomad ASJ AF: 0.627

Gnomad EAS AF: 0.716

Gnomad SAS AF: 0.636

Gnomad FIN AF: 0.552

Gnomad MID AF: 0.573

Gnomad NFE AF: 0.553

Gnomad OTH AF: 0.552

GnomAD2 exomes AF: 0.588 AC: 147809 AN: 251440 AF XY: 0.589

Gnomad AFR exome AF: 0.519

Gnomad AMR exome AF: 0.645

Gnomad ASJ exome AF: 0.628

Gnomad EAS exome AF: 0.716

Gnomad FIN exome AF: 0.553

Gnomad NFE exome AF: 0.553

Gnomad OTH exome AF: 0.566

GnomAD4 exome AF: 0.561 AC: 818657 AN: 1458364 Hom.: 231546 Cov.: 34 AF XY: 0.565 AC XY: 409847 AN XY: 725660

African (AFR) AF: 0.511 AC: 17059 AN: 33398

American (AMR) AF: 0.639 AC: 28593 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.627 AC: 16375 AN: 26100

East Asian (EAS) AF: 0.719 AC: 28521 AN: 39678

South Asian (SAS) AF: 0.637 AC: 54899 AN: 86210

European-Finnish (FIN) AF: 0.550 AC: 29379 AN: 53408

Middle Eastern (MID) AF: 0.619 AC: 3561 AN: 5750

European-Non Finnish (NFE) AF: 0.546 AC: 605724 AN: 1108830

Other (OTH) AF: 0.573 AC: 34546 AN: 60270

GnomAD4 genome AF: 0.554 AC: 84203 AN: 151942 Hom.: 23580 Cov.: 31 AF XY: 0.557 AC XY: 41388 AN XY: 74254

African (AFR) AF: 0.518 AC: 21473 AN: 41452

American (AMR) AF: 0.578 AC: 8807 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.627 AC: 2173 AN: 3468

East Asian (EAS) AF: 0.717 AC: 3677 AN: 5126

South Asian (SAS) AF: 0.635 AC: 3058 AN: 4816

European-Finnish (FIN) AF: 0.552 AC: 5836 AN: 10568

Middle Eastern (MID) AF: 0.578 AC: 170 AN: 294

European-Non Finnish (NFE) AF: 0.553 AC: 37589 AN: 67962

Other (OTH) AF: 0.550 AC: 1158 AN: 2106

Alfa AF: 0.557 Hom.: 36192

Bravo AF: 0.553

Asia WGS AF: 0.619 AC: 2154 AN: 3478

EpiCase AF: 0.555

EpiControl AF: 0.552

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	Hydatidiform mole, recurrent, 1 (3)
-	-	1	Hydatidiform mole (1)
-	-	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	0.23
DANN	Benign	0.27
PhyloP100		-0.26
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: rs269951; hg19: chr19-55441995; COSMIC: COSV60172236;