rs9936269

Variant names:

• chr16-57037668-G-A
• rs9936269
• NM_001384950.1:c.2801+384G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001384950.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NLRC5	NM_001384950.1	MANE Select	c.2801+384G>A		intron	N/A	NP_001371879.1
	NLRC5	NM_032206.5		c.2801+384G>A		intron	N/A	NP_115582.4
	NLRC5	NM_001384952.1		c.2801+384G>A		intron	N/A	NP_001371881.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NLRC5	ENST00000688547.1	MANE Select	c.2801+384G>A		intron	N/A	ENSP00000509992.1
	NLRC5	ENST00000262510.10	TSL:5	c.2801+384G>A		intron	N/A	ENSP00000262510.6
	NLRC5	ENST00000539144.5	TSL:5	c.2801+384G>A		intron	N/A	ENSP00000441727.1

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

African (AFR) AF: 0.200 AC: 8310 AN: 41466

American (AMR) AF: 0.0856 AC: 1309 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.153 AC: 529 AN: 3466

East Asian (EAS) AF: 0.00135 AC: 7 AN: 5188

South Asian (SAS) AF: 0.0642 AC: 309 AN: 4814

European-Finnish (FIN) AF: 0.180 AC: 1902 AN: 10558

Middle Eastern (MID) AF: 0.190 AC: 56 AN: 294

European-Non Finnish (NFE) AF: 0.110 AC: 7458 AN: 67990

Other (OTH) AF: 0.128 AC: 271 AN: 2112

Alfa AF: 0.117 Hom.: 649

Bravo AF: 0.129

Asia WGS AF: 0.0510 AC: 179 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.24
DANN	Benign	0.52
PhyloP100		-0.43
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs9936269; hg19: chr16-57071580;