rs775870

Variant names:

• chr19-54927800-C-G
• rs775870
• NM_001127255.2:c.2811-25G>C

Your query was ambiguous. Multiple possible variants found:

• chr19-54927800-C-G
• chr19-54927800-C-A
• chr19-54927800-C-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.2811-25G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0171 in 1,605,804 control chromosomes in the GnomAD database, including 1,674 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.060 (627 hom., cov: 33)
  • Exomes 𝑓: 0.013 (1047 hom.)
• Consequence: NLRP7 NM_001127255.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2 O:1
• Conservation: PhyloP100: -0.186
• Publications: 3 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=-0.9).
• BP6: Variant 19-54927800-C-G is Benign according to our data. Variant chr19-54927800-C-G is described in ClinVar as Benign. ClinVar VariationId is 97770.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.158 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.2811-25G>C		intron	N/A	NP_001120727.1	Q8WX94-3
	NLRP7	NM_001405531.1		c.2811-25G>C		intron	N/A	NP_001392460.1	Q8WX94-3
	NLRP7	NM_139176.4		c.2727-25G>C		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.2811-25G>C		intron	N/A	ENSP00000468706.1	Q8WX94-3
	NLRP7	ENST00000588756.5	TSL:1	c.2811-25G>C		intron	N/A	ENSP00000467123.1	Q8WX94-3
	NLRP7	ENST00000340844.6	TSL:1	c.2810+2699G>C		intron	N/A	ENSP00000339491.2	Q8WX94-1

Frequencies

GnomAD3 genomes AF: 0.0597 AC: 9073 AN: 152036 Hom.: 627 Cov.: 33

Gnomad AFR AF: 0.161

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0886

Gnomad ASJ AF: 0.00317

Gnomad EAS AF: 0.112

Gnomad SAS AF: 0.00851

Gnomad FIN AF: 0.0141

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.00247

Gnomad OTH AF: 0.0575

GnomAD2 exomes AF: 0.0386 AC: 9704 AN: 251258 AF XY: 0.0303

Gnomad AFR exome AF: 0.166

Gnomad AMR exome AF: 0.116

Gnomad ASJ exome AF: 0.00268

Gnomad EAS exome AF: 0.114

Gnomad FIN exome AF: 0.0146

Gnomad NFE exome AF: 0.00260

Gnomad OTH exome AF: 0.0264

GnomAD4 exome AF: 0.0126 AC: 18381 AN: 1453650 Hom.: 1047 Cov.: 32 AF XY: 0.0114 AC XY: 8217 AN XY: 723842

African (AFR) AF: 0.168 AC: 5602 AN: 33262

American (AMR) AF: 0.111 AC: 4948 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.00219 AC: 57 AN: 26060

East Asian (EAS) AF: 0.0920 AC: 3644 AN: 39616

South Asian (SAS) AF: 0.00418 AC: 360 AN: 86036

European-Finnish (FIN) AF: 0.0150 AC: 799 AN: 53320

Middle Eastern (MID) AF: 0.0189 AC: 108 AN: 5708

European-Non Finnish (NFE) AF: 0.00128 AC: 1410 AN: 1104840

Other (OTH) AF: 0.0242 AC: 1453 AN: 60100

GnomAD4 genome AF: 0.0599 AC: 9108 AN: 152154 Hom.: 627 Cov.: 33 AF XY: 0.0600 AC XY: 4467 AN XY: 74428

African (AFR) AF: 0.161 AC: 6676 AN: 41492

American (AMR) AF: 0.0889 AC: 1356 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.00317 AC: 11 AN: 3472

East Asian (EAS) AF: 0.112 AC: 578 AN: 5176

South Asian (SAS) AF: 0.00810 AC: 39 AN: 4814

European-Finnish (FIN) AF: 0.0141 AC: 150 AN: 10616

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.00247 AC: 168 AN: 68012

Other (OTH) AF: 0.0583 AC: 123 AN: 2110

Alfa AF: 0.0104 Hom.: 17

Bravo AF: 0.0708

Asia WGS AF: 0.0660 AC: 231 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.0
DANN	Benign	0.36
PhyloP100		-0.19
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: rs775870; hg19: chr19-55439168; COSMIC: COSV60179151;