rs61063081

Variant names:

• chr11-7038750-G-A
• rs61063081
• NM_176822.4:c.164G>A

Your query was ambiguous. Multiple possible variants found:

• chr11-7038750-G-A
• chr11-7038750-G-C
• chr11-7038750-G-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_176822.4(NLRP14):​c.164G>A​(p.Arg55Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.19 in 1,613,480 control chromosomes in the GnomAD database, including 31,931 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.15 (2153 hom., cov: 32)
  • Exomes 𝑓: 0.19 (29778 hom.)
• Consequence: NLRP14 NM_176822.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.358
• Publications: 19 publications found

Genes affected

NLRP14 (HGNC:22939): (NLR family pyrin domain containing 14) The protein encoded by this gene belongs to the NALP protein family. Members of the NALP protein family typically contain a NACHT domain, a NACHT-associated domain (NAD), a C-terminal leucine-rich repeat (LRR) region, and an N-terminal pyrin domain (PYD). This protein may play a regulatory role in the innate immune system as similar family members belong to the signal-induced multiprotein complex, the inflammasome, that activates the pro-inflammatory caspases, caspase-1 and caspase-5. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0010732114).
• BP6: Variant 11-7038750-G-A is Benign according to our data. Variant chr11-7038750-G-A is described in ClinVar as Benign. ClinVar VariationId is 1245032.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.21 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_176822.4. 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
	NLRP14	NM_176822.4	MANE Select	c.164G>A	p.Arg55Gln	missense	Exon 2 of 12	NP_789792.1	Q86W24

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NLRP14	ENST00000299481.5	TSL:5 MANE Select	c.164G>A	p.Arg55Gln	missense	Exon 2 of 12	ENSP00000299481.5	Q86W24
	NLRP14	ENST00000892206.1		c.164G>A	p.Arg55Gln	missense	Exon 2 of 11	ENSP00000562265.1

Frequencies

GnomAD3 genomes AF: 0.151 AC: 23020 AN: 152088 Hom.: 2153 Cov.: 32

Gnomad AFR AF: 0.0813

Gnomad AMI AF: 0.242

Gnomad AMR AF: 0.152

Gnomad ASJ AF: 0.201

Gnomad EAS AF: 0.0148

Gnomad SAS AF: 0.0854

Gnomad FIN AF: 0.0970

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.213

Gnomad OTH AF: 0.184

GnomAD2 exomes AF: 0.148 AC: 37151 AN: 250728 AF XY: 0.151

Gnomad AFR exome AF: 0.0774

Gnomad AMR exome AF: 0.109

Gnomad ASJ exome AF: 0.192

Gnomad EAS exome AF: 0.0151

Gnomad FIN exome AF: 0.103

Gnomad NFE exome AF: 0.210

Gnomad OTH exome AF: 0.178

GnomAD4 exome AF: 0.194 AC: 284024 AN: 1461274 Hom.: 29778 Cov.: 36 AF XY: 0.193 AC XY: 140056 AN XY: 726924

African (AFR) AF: 0.0781 AC: 2612 AN: 33464

American (AMR) AF: 0.116 AC: 5191 AN: 44700

Ashkenazi Jewish (ASJ) AF: 0.194 AC: 5072 AN: 26134

East Asian (EAS) AF: 0.0189 AC: 750 AN: 39700

South Asian (SAS) AF: 0.0987 AC: 8510 AN: 86196

European-Finnish (FIN) AF: 0.108 AC: 5751 AN: 53400

Middle Eastern (MID) AF: 0.173 AC: 995 AN: 5768

European-Non Finnish (NFE) AF: 0.220 AC: 244120 AN: 1111544

Other (OTH) AF: 0.183 AC: 11023 AN: 60368

GnomAD4 genome AF: 0.151 AC: 23026 AN: 152206 Hom.: 2153 Cov.: 32 AF XY: 0.145 AC XY: 10770 AN XY: 74410

African (AFR) AF: 0.0814 AC: 3378 AN: 41524

American (AMR) AF: 0.151 AC: 2311 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.201 AC: 697 AN: 3466

East Asian (EAS) AF: 0.0151 AC: 78 AN: 5178

South Asian (SAS) AF: 0.0859 AC: 414 AN: 4820

European-Finnish (FIN) AF: 0.0970 AC: 1029 AN: 10608

Middle Eastern (MID) AF: 0.190 AC: 56 AN: 294

European-Non Finnish (NFE) AF: 0.213 AC: 14460 AN: 68014

Other (OTH) AF: 0.182 AC: 383 AN: 2110

Alfa AF: 0.189 Hom.: 10127

Bravo AF: 0.154

TwinsUK AF: 0.218 AC: 810

ALSPAC AF: 0.218 AC: 840

ESP6500AA AF: 0.0841 AC: 370

ESP6500EA AF: 0.214 AC: 1840

ExAC AF: 0.149 AC: 18152

Asia WGS AF: 0.0550 AC: 193 AN: 3478

EpiCase AF: 0.222

EpiControl AF: 0.226

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	NLRP14-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.64	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.024	T
Eigen	Benign	-0.067
Eigen_PC	Benign	-0.26
FATHMM_MKL	Benign	0.042	N
LIST_S2	Benign	0.70	T
MetaRNN	Benign	0.0011	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.8	M
PhyloP100		0.36
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.21
Sift	Benign	0.39	T
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.30
MPC		0.15
ClinPred		0.077	T
GERP RS		2.2
Varity_R		0.33
gMVP		0.25
Mutation Taster		=96/4	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: rs61063081; hg19: chr11-7059981; COSMIC: COSV100205540;