11-7039005-TG-T

Position:

• chr11-7039005-TG-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_176822.4(NLRP14):​c.289+131del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.644 in 848,710 control chromosomes in the GnomAD database, including 176,586 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.62 (29675 hom., cov: 0)
  • Exomes 𝑓: 0.65 (146911 hom.)
• Consequence: NLRP14 NM_176822.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.810

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

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 11-7039005-TG-T is Benign according to our data. Variant chr11-7039005-TG-T is described in ClinVar as [Benign]. Clinvar id is 1278365.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.719 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NLRP14	NM_176822.4	c.289+131del		intron_variant		ENST00000299481.5	NP_789792.1
NLRP14	XM_011520044.2	c.289+131del		intron_variant			XP_011518346.1
NLRP14	XM_047426867.1	c.289+131del		intron_variant			XP_047282823.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NLRP14	ENST00000299481.5	c.289+131del		intron_variant		5	NM_176822.4	ENSP00000299481	P1

Frequencies

GnomAD3 genomes AF: 0.622 AC: 94381 AN: 151682 Hom.: 29653 Cov.: 0

Gnomad AFR AF: 0.541

Gnomad AMI AF: 0.606

Gnomad AMR AF: 0.629

Gnomad ASJ AF: 0.642

Gnomad EAS AF: 0.738

Gnomad SAS AF: 0.677

Gnomad FIN AF: 0.727

Gnomad MID AF: 0.621

Gnomad NFE AF: 0.641

Gnomad OTH AF: 0.607

GnomAD4 exome AF: 0.648 AC: 451932 AN: 696910 Hom.: 146911 AF XY: 0.649 AC XY: 231193 AN XY: 356428

Gnomad4 AFR exome AF: 0.544

Gnomad4 AMR exome AF: 0.620

Gnomad4 ASJ exome AF: 0.648

Gnomad4 EAS exome AF: 0.706

Gnomad4 SAS exome AF: 0.674

Gnomad4 FIN exome AF: 0.724

Gnomad4 NFE exome AF: 0.643

Gnomad4 OTH exome AF: 0.639

GnomAD4 genome AF: 0.622 AC: 94446 AN: 151800 Hom.: 29675 Cov.: 0 AF XY: 0.626 AC XY: 46478 AN XY: 74194

Gnomad4 AFR AF: 0.540

Gnomad4 AMR AF: 0.629

Gnomad4 ASJ AF: 0.642

Gnomad4 EAS AF: 0.738

Gnomad4 SAS AF: 0.677

Gnomad4 FIN AF: 0.727

Gnomad4 NFE AF: 0.641

Gnomad4 OTH AF: 0.611

Alfa AF: 0.439 Hom.: 1426

Bravo AF: 0.611

Asia WGS AF: 0.692 AC: 2407 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

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

Publications

LitVar

Other links and lift over

dbSNP: rs11288450; hg19: chr11-7060236;