16-57040539-T-C

Variant names:

• chr16-57040539-T-C
• rs289726
• NM_001384950.1:c.2871-111T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001384950.1(NLRC5):​c.2871-111T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.603 in 1,031,088 control chromosomes in the GnomAD database, including 191,678 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 0.55 (23928 hom., cov: 32)
  • Exomes 𝑓: 0.61 (167750 hom.)
• Consequence: NLRC5 NM_001384950.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.729
• Publications: 14 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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.637 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NLRC5	NM_001384950.1	c.2871-111T>C		intron_variant	Intron 16 of 48	ENST00000688547.1	NP_001371879.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NLRC5	ENST00000688547.1	c.2871-111T>C		intron_variant	Intron 16 of 48		NM_001384950.1	ENSP00000509992.1

Frequencies

GnomAD3 genomes AF: 0.548 AC: 83256 AN: 151838 Hom.: 23909 Cov.: 32

Gnomad AFR AF: 0.389

Gnomad AMI AF: 0.689

Gnomad AMR AF: 0.552

Gnomad ASJ AF: 0.690

Gnomad EAS AF: 0.403

Gnomad SAS AF: 0.487

Gnomad FIN AF: 0.598

Gnomad MID AF: 0.579

Gnomad NFE AF: 0.642

Gnomad OTH AF: 0.566

GnomAD4 exome AF: 0.613 AC: 538919 AN: 879132 Hom.: 167750 AF XY: 0.610 AC XY: 276019 AN XY: 452530

African (AFR) AF: 0.392 AC: 8660 AN: 22094

American (AMR) AF: 0.547 AC: 21048 AN: 38480

Ashkenazi Jewish (ASJ) AF: 0.675 AC: 13472 AN: 19972

East Asian (EAS) AF: 0.415 AC: 15153 AN: 36506

South Asian (SAS) AF: 0.504 AC: 34999 AN: 69396

European-Finnish (FIN) AF: 0.601 AC: 26770 AN: 44520

Middle Eastern (MID) AF: 0.605 AC: 2749 AN: 4542

European-Non Finnish (NFE) AF: 0.649 AC: 391393 AN: 602790

Other (OTH) AF: 0.604 AC: 24675 AN: 40832

GnomAD4 genome AF: 0.548 AC: 83307 AN: 151956 Hom.: 23928 Cov.: 32 AF XY: 0.544 AC XY: 40406 AN XY: 74262

African (AFR) AF: 0.389 AC: 16105 AN: 41420

American (AMR) AF: 0.552 AC: 8421 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.690 AC: 2391 AN: 3466

East Asian (EAS) AF: 0.403 AC: 2078 AN: 5150

South Asian (SAS) AF: 0.488 AC: 2350 AN: 4816

European-Finnish (FIN) AF: 0.598 AC: 6325 AN: 10570

Middle Eastern (MID) AF: 0.592 AC: 174 AN: 294

European-Non Finnish (NFE) AF: 0.642 AC: 43632 AN: 67950

Other (OTH) AF: 0.570 AC: 1204 AN: 2114

Alfa AF: 0.611 Hom.: 125893

Bravo AF: 0.539

Asia WGS AF: 0.475 AC: 1653 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	8.3
DANN	Benign	0.71
PhyloP100		0.73
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs289726; hg19: chr16-57074451; COSMIC: COSV52650976; COSMIC: COSV52650976;