Genetic Variant NM_001394894.2:c.-62-145C>A (chr19-55818381-G-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001394894.2(NLRP11):c.-62-145C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0968 in 555,404 control chromosomes in the GnomAD database, including 3,073 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.081 ( 642 hom., cov: 32)

Exomes 𝑓: 0.10 ( 2431 hom. )

Consequence

NLRP11
NM_001394894.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.335

Publications

10 publications found

Variant links:

Genes affected

NLRP11 (HGNC:22945): (NLR family pyrin domain containing 11) This gene is a member of the the NOD-like receptor protein (NLRP) gene family and encodes a protein with an N-terminal pyrin death (PYD) domain and nucleoside triphosphate hydrolase (NACHT) domain and a C-terminal leucine-rich repeats (LRR) region. This gene has been shown to regulate caspases in the proinflammatory signal transduction pathway and, based on studies of other members of the NLRP gene family with similar domain structure, is predicted to form part of the multiprotein inflammasome complex. Alternative splicing produces multiple transcript variants encoding distince isoforms. [provided by RefSeq, May 2017]

NLRP11 Gene-Disease associations (from GenCC):

Tourette syndrome
Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

NLRP11 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.93).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.125 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NLRP11	NM_001394894.2 link	c.-62-145C>A		intron_variant	Intron 1 of 9	ENST00000589093.6	NP_001381823.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NLRP11	ENST00000589093.6 link	c.-62-145C>A		intron_variant	Intron 1 of 9	1	NM_001394894.2	ENSP00000466285.1		P59045-1

Frequencies

GnomAD3 genomes

AF:

0.0814

AC:

12382

AN:

152112

Hom.:

642

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0241

Gnomad AMI

AF:

0.134

Gnomad AMR

AF:

0.0427

Gnomad ASJ

AF:

0.0706

Gnomad EAS

AF:

0.133

Gnomad SAS

AF:

0.0974

Gnomad FIN

AF:

0.155

Gnomad MID

AF:

0.0886

Gnomad NFE

AF:

0.109

Gnomad OTH

AF:

0.0707

GnomAD4 exome

AF:

0.103

AC:

41372

AN:

403174

Hom.:

2431

AF XY:

0.100

AC XY:

21183

AN XY:

210894

show subpopulations

African (AFR)

AF:

0.0225

AC:

260

AN:

11576

American (AMR)

AF:

0.0414

AC:

626

AN:

15112

Ashkenazi Jewish (ASJ)

AF:

0.0671

AC:

855

AN:

12738

East Asian (EAS)

AF:

0.145

AC:

4097

AN:

28332

South Asian (SAS)

AF:

0.0779

AC:

2873

AN:

36860

European-Finnish (FIN)

AF:

0.144

AC:

3813

AN:

26528

Middle Eastern (MID)

AF:

0.0524

AC:

AN:

1774

European-Non Finnish (NFE)

AF:

0.108

AC:

26708

AN:

246496

Other (OTH)

AF:

0.0862

AC:

2047

AN:

23758

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1692

3383

5075

6766

8458

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

152

304

456

608

760

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0813

AC:

12380

AN:

152230

Hom.:

642

Cov.:

AF XY:

0.0834

AC XY:

6209

AN XY:

74422

show subpopulations

African (AFR)

AF:

0.0241

AC:

1003

AN:

41540

American (AMR)

AF:

0.0427

AC:

653

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.0706

AC:

245

AN:

3470

East Asian (EAS)

AF:

0.133

AC:

688

AN:

5182

South Asian (SAS)

AF:

0.0971

AC:

468

AN:

4820

European-Finnish (FIN)

AF:

0.155

AC:

1645

AN:

10582

Middle Eastern (MID)

AF:

0.0884

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.109

AC:

7383

AN:

68020

Other (OTH)

AF:

0.0695

AC:

147

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

600

1200

1800

2400

3000

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

162

324

486

648

810

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0962

Hom.:

2347

Bravo

AF:

0.0702

Asia WGS

AF:

0.0990

AC:

345

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

1.9

(source)

DANN

Benign

0.53

PhyloP100

-0.34

PromoterAI

-0.014

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over