rs141755467

Variant names:

• chr11-280403-G-C
• rs141755467
• NM_001276700.2:c.669G>C

Your query was ambiguous. Multiple possible variants found:

• chr11-280403-G-C
• chr11-280403-G-A

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001276700.2(NLRP6):​c.669G>C​(p.Lys223Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00187 in 1,578,840 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

• Frequency:
  • Genomes: 𝑓 0.0011 (0 hom., cov: 34)
  • Exomes 𝑓: 0.0020 (7 hom.)
• Consequence: NLRP6 NM_001276700.2 missense
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:2
• Conservation: PhyloP100: -0.0490
• Publications: 2 publications found

Genes affected

NLRP6 (HGNC:22944): (NLR family pyrin domain containing 6) The protein encoded by this gene binds arginine-vasopressin and may be involved in the arginine-vasopressin-mediated regulation of renal salt-water balance. The encoded protein also mediates inflammatory responses in the colon to allow recovery from intestinal epithelial damage and protects against tumorigenesis and the development of colitis. Finally, this protein can increase activation of NF-kappa-B, activation of CASP1 through interaction with ASC, and cAMP accumulation. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Feb 2013]

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.010453165).
• BS2: High Homozygotes in GnomAdExome4 at 7 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001276700.2. 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
	NLRP6	NM_001276700.2	MANE Select	c.669G>C	p.Lys223Asn	missense	Exon 4 of 8	NP_001263629.1	P59044-2
	NLRP6	NM_138329.2		c.669G>C	p.Lys223Asn	missense	Exon 4 of 8	NP_612202.2	P59044-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NLRP6	ENST00000534750.6	TSL:2 MANE Select	c.669G>C	p.Lys223Asn	missense	Exon 4 of 8	ENSP00000433617.1	P59044-2
	NLRP6	ENST00000312165.5	TSL:1	c.669G>C	p.Lys223Asn	missense	Exon 4 of 8	ENSP00000309767.4	P59044-1

Frequencies

GnomAD3 genomes AF: 0.00109 AC: 166 AN: 152204 Hom.: 0 Cov.: 34

Gnomad AFR AF: 0.000386

Gnomad AMI AF: 0.00658

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000377

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00203

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.00112 AC: 221 AN: 197296 AF XY: 0.00110

Gnomad AFR exome AF: 0.000254

Gnomad AMR exome AF: 0.000125

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000116

Gnomad NFE exome AF: 0.00240

Gnomad OTH exome AF: 0.000596

GnomAD4 exome AF: 0.00196 AC: 2790 AN: 1426528 Hom.: 7 Cov.: 70 AF XY: 0.00185 AC XY: 1310 AN XY: 708862

African (AFR) AF: 0.000250 AC: 8 AN: 32058

American (AMR) AF: 0.000210 AC: 9 AN: 42790

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25598

East Asian (EAS) AF: 0.00 AC: 0 AN: 38308

South Asian (SAS) AF: 0.0000120 AC: 1 AN: 83488

European-Finnish (FIN) AF: 0.000383 AC: 14 AN: 36590

Middle Eastern (MID) AF: 0.000698 AC: 4 AN: 5728

European-Non Finnish (NFE) AF: 0.00243 AC: 2685 AN: 1102710

Other (OTH) AF: 0.00116 AC: 69 AN: 59258

GnomAD4 genome AF: 0.00109 AC: 166 AN: 152312 Hom.: 0 Cov.: 34 AF XY: 0.00105 AC XY: 78 AN XY: 74492

African (AFR) AF: 0.000385 AC: 16 AN: 41574

American (AMR) AF: 0.0000653 AC: 1 AN: 15308

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.000377 AC: 4 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 290

European-Non Finnish (NFE) AF: 0.00203 AC: 138 AN: 68012

Other (OTH) AF: 0.000473 AC: 1 AN: 2112

Alfa AF: 0.00128 Hom.: 0

Bravo AF: 0.00111

TwinsUK AF: 0.00135 AC: 5

ALSPAC AF: 0.00182 AC: 7

ESP6500AA AF: 0.000456 AC: 2

ESP6500EA AF: 0.00221 AC: 19

ExAC AF: 0.00117 AC: 138

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	2	-	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.80
BayesDel_addAF	Benign	-0.40	T
BayesDel_noAF	Benign	-0.35
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.092	T
Eigen	Benign	-0.26
Eigen_PC	Benign	-0.34
FATHMM_MKL	Benign	0.083	N
LIST_S2	Benign	0.64	T
M_CAP	Pathogenic	0.32	D
MetaRNN	Benign	0.010	T
MetaSVM	Uncertain	-0.23	T
PhyloP100		-0.049
PrimateAI	Uncertain	0.74	T
PROVEAN	Benign	-0.46	N
REVEL	Uncertain	0.35
Sift	Uncertain	0.0080	D
Sift4G	Uncertain	0.0090	D
Polyphen		1.0	D
Vest4		0.30
MutPred		0.61		Loss of ubiquitination at K223 (P = 0.0233)
MVP		0.11
ClinPred		0.055	T
GERP RS		2.5
Varity_R		0.36
gMVP		0.85
Mutation Taster		=93/7	polymorphism

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: rs141755467; hg19: chr11-280403;