rs9936269

Positions:

• chr16-57037668-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.2801+384G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.133 in 152,084 control chromosomes in the GnomAD database, including 1,614 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 0.13 (1614 hom., cov: 32)
• Consequence: NLRC5 NM_001384950.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.433

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.197 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NLRC5	NM_001384950.1	c.2801+384G>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.2801+384G>A		intron_variant			NM_001384950.1	ENSP00000509992	P2

Frequencies

GnomAD3 genomes AF: 0.133 AC: 20265 AN: 151966 Hom.: 1609 Cov.: 32

Gnomad AFR AF: 0.200

Gnomad AMI AF: 0.155

Gnomad AMR AF: 0.0858

Gnomad ASJ AF: 0.153

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.0650

Gnomad FIN AF: 0.180

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.110

Gnomad OTH AF: 0.130

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

GnomAD4 genome AF: 0.133 AC: 20292 AN: 152084 Hom.: 1614 Cov.: 32 AF XY: 0.133 AC XY: 9854 AN XY: 74344

Gnomad4 AFR AF: 0.200

Gnomad4 AMR AF: 0.0856

Gnomad4 ASJ AF: 0.153

Gnomad4 EAS AF: 0.00135

Gnomad4 SAS AF: 0.0642

Gnomad4 FIN AF: 0.180

Gnomad4 NFE AF: 0.110

Gnomad4 OTH AF: 0.128

Alfa AF: 0.116 Hom.: 586

Bravo AF: 0.129

Asia WGS AF: 0.0510 AC: 179 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.24
DANN	Benign	0.52

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: rs9936269; hg19: chr16-57071580;