chr16-70654610-A-G

Position:

• chr16-70654610-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001393494.1(IL34):​c.101A>G​(p.Glu34Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: IL34 NM_001393494.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.42

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.36233473).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL34	NM_001393494.1	c.101A>G	p.Glu34Gly	missense_variant	2/6	ENST00000288098.7	NP_001380423.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL34	ENST00000288098.7	c.101A>G	p.Glu34Gly	missense_variant	2/6	1	NM_001393494.1	ENSP00000288098	P2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 25, 2023

The c.101A>G (p.E34G) alteration is located in exon 3 (coding exon 2) of the IL34 gene. This alteration results from a A to G substitution at nucleotide position 101, causing the glutamic acid (E) at amino acid position 34 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Benign	-0.082	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.055	T;.;T;T
Eigen	Uncertain	0.35
Eigen_PC	Uncertain	0.26
FATHMM_MKL	Benign	0.73	D
LIST_S2	Benign	0.58	T;T;.;T
M_CAP	Benign	0.051	D
MetaRNN	Benign	0.36	T;T;T;T
MetaSVM	Benign	-0.50	T
MutationAssessor	Benign	1.8	L;.;L;.
MutationTaster	Benign	0.97	D;D;D
PrimateAI	Benign	0.35	T
PROVEAN	Pathogenic	-4.9	D;D;D;.
REVEL	Benign	0.18
Sift	Benign	0.032	D;D;D;.
Sift4G	Uncertain	0.0040	D;D;D;D
Polyphen		0.98	D;.;D;.
Vest4		0.25
MutPred		0.33		Loss of stability (P = 0.0385);Loss of stability (P = 0.0385);Loss of stability (P = 0.0385);.;
MVP		0.65
MPC		0.059
ClinPred		0.91	D
GERP RS		4.8
Varity_R		0.31
gMVP		0.38

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: rs1044929627; hg19: chr16-70688513;