16-57040539-T-C

Position:

• chr16-57040539-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001384950.1(NLRC5):​c.2871-111T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.603 in 1,031,088 control chromosomes in the GnomAD database, including 191,678 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 0.55 (23928 hom., cov: 32)
  • Exomes 𝑓: 0.61 (167750 hom.)
• Consequence: NLRC5 NM_001384950.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.729

Genes affected

NLRC5 (HGNC:29933): (NLR family CARD domain containing 5) This gene encodes a member of the caspase recruitment domain-containing NLR family. This gene plays a role in cytokine response and antiviral immunity through its inhibition of NF-kappa-B activation and negative regulation of type I interferon signaling pathways. [provided by RefSeq, Oct 2011]

NLRC5 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.637 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NLRC5	NM_001384950.1	c.2871-111T>C		intron_variant		ENST00000688547.1	NP_001371879.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NLRC5	ENST00000688547.1	c.2871-111T>C		intron_variant			NM_001384950.1	ENSP00000509992.1

Frequencies

GnomAD3 genomes AF: 0.548 AC: 83256 AN: 151838 Hom.: 23909 Cov.: 32

Gnomad AFR AF: 0.389

Gnomad AMI AF: 0.689

Gnomad AMR AF: 0.552

Gnomad ASJ AF: 0.690

Gnomad EAS AF: 0.403

Gnomad SAS AF: 0.487

Gnomad FIN AF: 0.598

Gnomad MID AF: 0.579

Gnomad NFE AF: 0.642

Gnomad OTH AF: 0.566

GnomAD4 exome AF: 0.613 AC: 538919 AN: 879132 Hom.: 167750 AF XY: 0.610 AC XY: 276019 AN XY: 452530

Gnomad4 AFR exome AF: 0.392

Gnomad4 AMR exome AF: 0.547

Gnomad4 ASJ exome AF: 0.675

Gnomad4 EAS exome AF: 0.415

Gnomad4 SAS exome AF: 0.504

Gnomad4 FIN exome AF: 0.601

Gnomad4 NFE exome AF: 0.649

Gnomad4 OTH exome AF: 0.604

GnomAD4 genome AF: 0.548 AC: 83307 AN: 151956 Hom.: 23928 Cov.: 32 AF XY: 0.544 AC XY: 40406 AN XY: 74262

Gnomad4 AFR AF: 0.389

Gnomad4 AMR AF: 0.552

Gnomad4 ASJ AF: 0.690

Gnomad4 EAS AF: 0.403

Gnomad4 SAS AF: 0.488

Gnomad4 FIN AF: 0.598

Gnomad4 NFE AF: 0.642

Gnomad4 OTH AF: 0.570

Alfa AF: 0.624 Hom.: 60250

Bravo AF: 0.539

Asia WGS AF: 0.475 AC: 1653 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	8.3
DANN	Benign	0.71

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs289726; hg19: chr16-57074451; COSMIC: COSV52650976; COSMIC: COSV52650976;