11-7038518-T-A

Position:

• chr11-7038518-T-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_176822.4(NLRP14):​c.-21-48T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0996 in 1,400,498 control chromosomes in the GnomAD database, including 7,661 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.099 (787 hom., cov: 32)
  • Exomes 𝑓: 0.10 (6874 hom.)
• Consequence: NLRP14 NM_176822.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.450

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 11-7038518-T-A is Benign according to our data. Variant chr11-7038518-T-A is described in ClinVar as [Benign]. Clinvar id is 1231883.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.156 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NLRP14	NM_176822.4	c.-21-48T>A		intron_variant		ENST00000299481.5	NP_789792.1
NLRP14	XM_011520044.2	c.-21-48T>A		intron_variant			XP_011518346.1
NLRP14	XM_047426867.1	c.-21-48T>A		intron_variant			XP_047282823.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NLRP14	ENST00000299481.5	c.-21-48T>A		intron_variant		5	NM_176822.4	ENSP00000299481.5

Frequencies

GnomAD3 genomes AF: 0.0987 AC: 15023 AN: 152174 Hom.: 788 Cov.: 32

Gnomad AFR AF: 0.0733

Gnomad AMI AF: 0.127

Gnomad AMR AF: 0.162

Gnomad ASJ AF: 0.0755

Gnomad EAS AF: 0.120

Gnomad SAS AF: 0.107

Gnomad FIN AF: 0.119

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.0959

Gnomad OTH AF: 0.0888

GnomAD4 exome AF: 0.0997 AC: 124418 AN: 1248206 Hom.: 6874 Cov.: 17 AF XY: 0.0988 AC XY: 62367 AN XY: 631410

Gnomad4 AFR exome AF: 0.0624

Gnomad4 AMR exome AF: 0.209

Gnomad4 ASJ exome AF: 0.0712

Gnomad4 EAS exome AF: 0.147

Gnomad4 SAS exome AF: 0.0954

Gnomad4 FIN exome AF: 0.113

Gnomad4 NFE exome AF: 0.0942

Gnomad4 OTH exome AF: 0.0982

GnomAD4 genome AF: 0.0986 AC: 15019 AN: 152292 Hom.: 787 Cov.: 32 AF XY: 0.102 AC XY: 7610 AN XY: 74462

Gnomad4 AFR AF: 0.0732

Gnomad4 AMR AF: 0.161

Gnomad4 ASJ AF: 0.0755

Gnomad4 EAS AF: 0.119

Gnomad4 SAS AF: 0.106

Gnomad4 FIN AF: 0.119

Gnomad4 NFE AF: 0.0959

Gnomad4 OTH AF: 0.0879

Alfa AF: 0.0969 Hom.: 107

Bravo AF: 0.0991

Asia WGS AF: 0.113 AC: 396 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.5
DANN	Benign	0.54

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: rs17279697; hg19: chr11-7059749; COSMIC: COSV55072231;