Genetic Variant NLRC5:c.-127-13083T>C (chr16-57003991-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001384950.1(NLRC5):c.-127-13083T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.709 in 152,094 control chromosomes in the GnomAD database, including 39,152 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 0.71 ( 39110 hom., cov: 30)

Exomes 𝑓: 0.84 ( 42 hom. )

Consequence

NLRC5
NM_001384950.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.21

Publications

4 publications found

Variant links:

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]

NLRC5 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.793 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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
NLRC5	NM_001384950.1	MANE Select	c.-127-13083T>C	intron	N/A	NP_001371879.1
NLRC5	NM_032206.5		c.-127-13083T>C	intron	N/A	NP_115582.4
NLRC5	NM_001384952.1		c.-127-13083T>C	intron	N/A	NP_001371881.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
NLRC5	ENST00000688547.1	MANE Select	c.-127-13083T>C	intron	N/A	ENSP00000509992.1
NLRC5	ENST00000544641.5	TSL:3	c.-232T>C	5_prime_UTR	Exon 1 of 3	ENSP00000439464.1
NLRC5	ENST00000262510.10	TSL:5	c.-127-13083T>C	intron	N/A	ENSP00000262510.6

Frequencies

GnomAD3 genomes

AF:

0.709

AC:

107729

AN:

151860

Hom.:

39075

Cov.:

show subpopulations

Gnomad AFR

AF:

0.557

Gnomad AMI

AF:

0.883

Gnomad AMR

AF:

0.719

Gnomad ASJ

AF:

0.851

Gnomad EAS

AF:

0.649

Gnomad SAS

AF:

0.583

Gnomad FIN

AF:

0.740

Gnomad MID

AF:

0.699

Gnomad NFE

AF:

0.798

Gnomad OTH

AF:

0.737

GnomAD4 exome

AF:

0.836

AC:

AN:

116

Hom.:

Cov.:

AF XY:

0.845

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.667

AC:

AN:

American (AMR)

AF:

0.750

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.500

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.643

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.900

AC:

AN:

Other (OTH)

AF:

0.800

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.594

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.709

AC:

107813

AN:

151978

Hom.:

39110

Cov.:

AF XY:

0.702

AC XY:

52157

AN XY:

74264

show subpopulations

African (AFR)

AF:

0.557

AC:

23075

AN:

41402

American (AMR)

AF:

0.719

AC:

10973

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.851

AC:

2948

AN:

3466

East Asian (EAS)

AF:

0.650

AC:

3345

AN:

5150

South Asian (SAS)

AF:

0.583

AC:

2802

AN:

4804

European-Finnish (FIN)

AF:

0.740

AC:

7819

AN:

10566

Middle Eastern (MID)

AF:

0.701

AC:

206

AN:

294

European-Non Finnish (NFE)

AF:

0.798

AC:

54290

AN:

68008

Other (OTH)

AF:

0.735

AC:

1550

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1505

3010

4515

6020

7525

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

828

1656

2484

3312

4140

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.768

Hom.:

172681

Bravo

AF:

0.706

Asia WGS

AF:

0.594

AC:

2065

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.059

(source)

DANN

Benign

0.41

PhyloP100

-3.2

PromoterAI

-0.0073

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over