rs16965220

Positions:

• chr16-57031209-C-A
• chr16-57031209-C-G

Variant summary

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

The NM_001384950.1(NLRC5):​c.2418-195C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.289 in 152,052 control chromosomes in the GnomAD database, including 6,618 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 0.29 (6618 hom., cov: 31)
• Consequence: NLRC5 NM_001384950.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0330

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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.317 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NLRC5	NM_001384950.1	c.2418-195C>A		intron_variant		ENST00000688547.1	NP_001371879.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NLRC5	ENST00000688547.1	c.2418-195C>A		intron_variant			NM_001384950.1	ENSP00000509992.1

Frequencies

GnomAD3 genomes AF: 0.289 AC: 43939 AN: 151934 Hom.: 6615 Cov.: 31

Gnomad AFR AF: 0.236

Gnomad AMI AF: 0.438

Gnomad AMR AF: 0.271

Gnomad ASJ AF: 0.452

Gnomad EAS AF: 0.198

Gnomad SAS AF: 0.298

Gnomad FIN AF: 0.281

Gnomad MID AF: 0.424

Gnomad NFE AF: 0.321

Gnomad OTH AF: 0.334

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

GnomAD4 genome AF: 0.289 AC: 43953 AN: 152052 Hom.: 6618 Cov.: 31 AF XY: 0.286 AC XY: 21251 AN XY: 74292

Gnomad4 AFR AF: 0.236

Gnomad4 AMR AF: 0.270

Gnomad4 ASJ AF: 0.452

Gnomad4 EAS AF: 0.198

Gnomad4 SAS AF: 0.299

Gnomad4 FIN AF: 0.281

Gnomad4 NFE AF: 0.321

Gnomad4 OTH AF: 0.334

Alfa AF: 0.321 Hom.: 16526

Bravo AF: 0.284

Asia WGS AF: 0.249 AC: 863 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.9
DANN	Benign	0.34

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: rs16965220; hg19: chr16-57065121;