chr16-70659729-A-G

Variant names:

• chr16-70659729-A-G
• rs770853044
• NM_001393494.1:c.514A>G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001393494.1(IL34):​c.514A>G​(p.Met172Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000187 in 1,606,570 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: IL34 NM_001393494.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.68

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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.762

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL34	NM_001393494.1	c.514A>G	p.Met172Val	missense_variant	Exon 5 of 6	ENST00000288098.7	NP_001380423.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL34	ENST00000288098.7	c.514A>G	p.Met172Val	missense_variant	Exon 5 of 6	1	NM_001393494.1	ENSP00000288098.2
IL34	ENST00000566361.1	c.439A>G	p.Met147Val	missense_variant	Exon 5 of 6	1		ENSP00000463886.1
IL34	ENST00000429149.6	c.514A>G	p.Met172Val	missense_variant	Exon 6 of 7	5		ENSP00000397863.2

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152202 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000138 AC: 2 AN: 1454368 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 723014

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.02e-7

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152202 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74352

Gnomad4 AFR AF: 0.0000241

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Bravo AF: 0.0000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.74
BayesDel_addAF	Uncertain	0.098	D
BayesDel_noAF	Benign	-0.10
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.21	T;T;T
Eigen	Uncertain	0.63
Eigen_PC	Uncertain	0.61
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.76	T;.;T
M_CAP	Benign	0.043	D
MetaRNN	Pathogenic	0.76	D;D;D
MetaSVM	Benign	-0.47	T
MutationAssessor	Benign	2.0	M;M;.
PrimateAI	Uncertain	0.66	T
PROVEAN	Uncertain	-3.2	D;D;.
REVEL	Benign	0.27
Sift	Uncertain	0.0070	D;D;.
Sift4G	Uncertain	0.014	D;D;D
Polyphen		0.96	D;D;.
Vest4		0.73
MutPred		0.29		Gain of sheet (P = 0.0101);Gain of sheet (P = 0.0101);.;
MVP		0.79
MPC		0.29
ClinPred		0.96	D
GERP RS		5.1
Varity_R		0.64
gMVP		0.52

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: rs770853044; hg19: chr16-70693632;