16-57013387-T-C

Position:

• chr16-57013387-T-C

Variant summary

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

The NM_001384950.1(NLRC5):​c.-127-3687T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0567 in 630,272 control chromosomes in the GnomAD database, including 1,151 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 0.055 (258 hom., cov: 34)
  • Exomes 𝑓: 0.057 (893 hom.)
• Consequence: NLRC5 NM_001384950.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.24

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]

CFAP69P1 (HGNC:50809): (CFAP69 pseudogene 1)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0855 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NLRC5	NM_001384950.1	c.-127-3687T>C		intron_variant		ENST00000688547.1	NP_001371879.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NLRC5	ENST00000688547.1	c.-127-3687T>C		intron_variant			NM_001384950.1	ENSP00000509992	P2
CFAP69P1	ENST00000566704.1	n.714A>G		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes AF: 0.0554 AC: 8426 AN: 152180 Hom.: 254 Cov.: 34

Gnomad AFR AF: 0.0612

Gnomad AMI AF: 0.0186

Gnomad AMR AF: 0.0335

Gnomad ASJ AF: 0.0550

Gnomad EAS AF: 0.0325

Gnomad SAS AF: 0.0921

Gnomad FIN AF: 0.0681

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0545

Gnomad OTH AF: 0.0526

GnomAD4 exome AF: 0.0571 AC: 27275 AN: 477974 Hom.: 893 Cov.: 0 AF XY: 0.0583 AC XY: 15036 AN XY: 258002

Gnomad4 AFR exome AF: 0.0622

Gnomad4 AMR exome AF: 0.0267

Gnomad4 ASJ exome AF: 0.0513

Gnomad4 EAS exome AF: 0.0358

Gnomad4 SAS exome AF: 0.0887

Gnomad4 FIN exome AF: 0.0697

Gnomad4 NFE exome AF: 0.0541

Gnomad4 OTH exome AF: 0.0534

GnomAD4 genome AF: 0.0554 AC: 8444 AN: 152298 Hom.: 258 Cov.: 34 AF XY: 0.0556 AC XY: 4141 AN XY: 74472

Gnomad4 AFR AF: 0.0614

Gnomad4 AMR AF: 0.0334

Gnomad4 ASJ AF: 0.0550

Gnomad4 EAS AF: 0.0326

Gnomad4 SAS AF: 0.0925

Gnomad4 FIN AF: 0.0681

Gnomad4 NFE AF: 0.0546

Gnomad4 OTH AF: 0.0535

Alfa AF: 0.0536 Hom.: 161

Bravo AF: 0.0515

Asia WGS AF: 0.0590 AC: 207 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	8.6
DANN	Benign	0.85

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: rs16965039; hg19: chr16-57047299;