rs289747

chr16-56990026-C-T

Variant summary

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

The NM_001384950.1(NLRC5):c.-128+409C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.384 in 152,110 control chromosomes in the GnomAD database, including 11,483 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 0.38 (11483 hom., cov: 33)
• Consequence: NLRC5 NM_001384950.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.378

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=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.43 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NLRC5	NM_001384950.1	c.-128+409C>T		intron_variant		ENST00000688547.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NLRC5	ENST00000688547.1	c.-128+409C>T		intron_variant			NM_001384950.1	P2

Frequencies

GnomAD3 genomes AF: 0.384 AC: 58363 AN: 151992 Hom.: 11474 Cov.: 33

Gnomad AFR AF: 0.435

Gnomad AMI AF: 0.439

Gnomad AMR AF: 0.339

Gnomad ASJ AF: 0.362

Gnomad EAS AF: 0.228

Gnomad SAS AF: 0.400

Gnomad FIN AF: 0.301

Gnomad MID AF: 0.396

Gnomad NFE AF: 0.387

Gnomad OTH AF: 0.375

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.384 AC: 58402 AN: 152110 Hom.: 11483 Cov.: 33 AF XY: 0.381 AC XY: 28296 AN XY: 74364

Gnomad4 AFR AF: 0.435

Gnomad4 AMR AF: 0.339

Gnomad4 ASJ AF: 0.362

Gnomad4 EAS AF: 0.229

Gnomad4 SAS AF: 0.401

Gnomad4 FIN AF: 0.301

Gnomad4 NFE AF: 0.387

Gnomad4 OTH AF: 0.370

Alfa AF: 0.388 Hom.: 23566

Bravo AF: 0.390

Asia WGS AF: 0.305 AC: 1063 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	7.0
Dann	Benign	0.62

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: rs289747; hg19: chr16-57023938;