Genetic Variant IL34:p.Arg88Gly (chr16-70656981-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001393494.1(IL34):c.262C>G(p.Arg88Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,457,856 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R88W) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

IL34
NM_001393494.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.99

Publications

0 publications found

Variant links:

Genes affected

IL34 (HGNC:28529): (interleukin 34) Interleukin-34 is a cytokine that promotes the differentiation and viability of monocytes and macrophages through the colony-stimulating factor-1 receptor (CSF1R; MIM 164770) (Lin et al., 2008 [PubMed 18467591]).[supplied by OMIM, May 2008]

IL34 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.1524365).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001393494.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
IL34	NM_001393494.1	MANE Select	c.262C>G	p.Arg88Gly	missense	Exon 4 of 6	NP_001380423.1	Q6ZMJ4-1
IL34	NM_001172772.2		c.262C>G	p.Arg88Gly	missense	Exon 5 of 7	NP_001166243.1	Q6ZMJ4-1
IL34	NM_001393493.1		c.262C>G	p.Arg88Gly	missense	Exon 5 of 7	NP_001380422.1	Q6ZMJ4-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
IL34	ENST00000288098.7	TSL:1 MANE Select	c.262C>G	p.Arg88Gly	missense	Exon 4 of 6	ENSP00000288098.2	Q6ZMJ4-1
IL34	ENST00000566361.1	TSL:1	c.187C>G	p.Arg63Gly	missense	Exon 4 of 6	ENSP00000463886.1	J3QQT3
IL34	ENST00000429149.6	TSL:5	c.262C>G	p.Arg88Gly	missense	Exon 5 of 7	ENSP00000397863.2	Q6ZMJ4-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.86e-7

AC:

AN:

1457856

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

724980

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33368

American (AMR)

AF:

0.00

AC:

AN:

44560

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26024

East Asian (EAS)

AF:

0.00

AC:

AN:

39670

South Asian (SAS)

AF:

0.0000116

AC:

AN:

85972

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53332

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4218

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1110604

Other (OTH)

AF:

0.00

AC:

AN:

60108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.675

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.45

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.038

Eigen

Benign

-0.0091

Eigen_PC

Benign

0.12

FATHMM_MKL

Benign

0.68

LIST_S2

Benign

0.75

M_CAP

Benign

0.023

MetaRNN

Benign

0.15

MetaSVM

Benign

-0.94

MutationAssessor

Benign

1.5

PhyloP100

2.0

PrimateAI

Benign

0.23

PROVEAN

Uncertain

-3.2

REVEL

Benign

0.061

Sift

Benign

0.13

Sift4G

Benign

0.35

Polyphen

0.13

Vest4

0.24

MutPred

0.24

Loss of MoRF binding (P = 0.0156)

MVP

0.53

MPC

0.13

ClinPred

0.83

GERP RS

4.2

Varity_R

0.28

gMVP

0.14

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over