rs17369578

Positions:

• chr16-56997899-G-A

Variant summary

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

The NM_001384950.1(NLRC5):​c.-128+8282G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0515 in 152,190 control chromosomes in the GnomAD database, including 262 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 0.051 (262 hom., cov: 31)
• Consequence: NLRC5 NM_001384950.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.373

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=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.152 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NLRC5	NM_001384950.1	c.-128+8282G>A		intron_variant		ENST00000688547.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NLRC5	ENST00000688547.1	c.-128+8282G>A		intron_variant			NM_001384950.1	P2
NLRC5	ENST00000262510.10	c.-128+8304G>A		intron_variant		5		P2
NLRC5	ENST00000539881.5	c.-128+8282G>A		intron_variant, NMD_transcript_variant		2
NLRC5	ENST00000538273.5	n.33+8304G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.0515 AC: 7831 AN: 152072 Hom.: 261 Cov.: 31

Gnomad AFR AF: 0.0437

Gnomad AMI AF: 0.0154

Gnomad AMR AF: 0.0303

Gnomad ASJ AF: 0.0357

Gnomad EAS AF: 0.0592

Gnomad SAS AF: 0.162

Gnomad FIN AF: 0.108

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.0451

Gnomad OTH AF: 0.0445

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

GnomAD4 genome AF: 0.0515 AC: 7833 AN: 152190 Hom.: 262 Cov.: 31 AF XY: 0.0559 AC XY: 4160 AN XY: 74404

Gnomad4 AFR AF: 0.0437

Gnomad4 AMR AF: 0.0302

Gnomad4 ASJ AF: 0.0357

Gnomad4 EAS AF: 0.0594

Gnomad4 SAS AF: 0.161

Gnomad4 FIN AF: 0.108

Gnomad4 NFE AF: 0.0451

Gnomad4 OTH AF: 0.0440

Alfa AF: 0.0528 Hom.: 146

Bravo AF: 0.0415

Asia WGS AF: 0.110 AC: 383 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.0
DANN	Benign	0.57

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: rs17369578; hg19: chr16-57031811;