rs1566439

Positions:

• chr16-56990750-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.-128+1133T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.371 in 152,000 control chromosomes in the GnomAD database, including 11,361 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 0.37 (11360 hom., cov: 31)
  • Exomes 𝑓: 0.50 (1 hom.)
• Consequence: NLRC5 NM_001384950.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.46

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.58 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NLRC5	NM_001384950.1	c.-128+1133T>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.-128+1133T>C		intron_variant			NM_001384950.1	ENSP00000509992	P2

Frequencies

GnomAD3 genomes AF: 0.371 AC: 56331 AN: 151874 Hom.: 11355 Cov.: 31

Gnomad AFR AF: 0.215

Gnomad AMI AF: 0.516

Gnomad AMR AF: 0.483

Gnomad ASJ AF: 0.407

Gnomad EAS AF: 0.599

Gnomad SAS AF: 0.397

Gnomad FIN AF: 0.472

Gnomad MID AF: 0.345

Gnomad NFE AF: 0.402

Gnomad OTH AF: 0.402

GnomAD4 exome AF: 0.500 AC: 4 AN: 8 Hom.: 1 Cov.: 0 AF XY: 0.500 AC XY: 2 AN XY: 4

Gnomad4 EAS exome AF: 1.00

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.250

GnomAD4 genome AF: 0.371 AC: 56365 AN: 151992 Hom.: 11360 Cov.: 31 AF XY: 0.378 AC XY: 28038 AN XY: 74270

Gnomad4 AFR AF: 0.215

Gnomad4 AMR AF: 0.483

Gnomad4 ASJ AF: 0.407

Gnomad4 EAS AF: 0.598

Gnomad4 SAS AF: 0.397

Gnomad4 FIN AF: 0.472

Gnomad4 NFE AF: 0.401

Gnomad4 OTH AF: 0.404

Alfa AF: 0.397 Hom.: 22888

Bravo AF: 0.366

Asia WGS AF: 0.482 AC: 1674 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.58
DANN	Benign	0.66

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: rs1566439; hg19: chr16-57024662;