16-70646954-C-T

Variant names:

• chr16-70646954-C-T
• rs772446015
• NM_001393494.1:c.7C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001393494.1(IL34):​c.7C>T​(p.Arg3Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000709 in 1,467,762 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000059 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000072 (0 hom.)
• Consequence: IL34 NM_001393494.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.129
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.07518995).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL34	NM_001393494.1	MANE Select	c.7C>T	p.Arg3Trp	missense	Exon 1 of 6	NP_001380423.1	Q6ZMJ4-1
	IL34	NM_001172772.2		c.7C>T	p.Arg3Trp	missense	Exon 2 of 7	NP_001166243.1	Q6ZMJ4-1
	IL34	NM_001393493.1		c.7C>T	p.Arg3Trp	missense	Exon 2 of 7	NP_001380422.1	Q6ZMJ4-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL34	ENST00000288098.7	TSL:1 MANE Select	c.7C>T	p.Arg3Trp	missense	Exon 1 of 6	ENSP00000288098.2	Q6ZMJ4-1
	IL34	ENST00000429149.6	TSL:5	c.7C>T	p.Arg3Trp	missense	Exon 2 of 7	ENSP00000397863.2	Q6ZMJ4-1
	IL34	ENST00000877106.1		c.7C>T	p.Arg3Trp	missense	Exon 2 of 7	ENSP00000547165.1

Frequencies

GnomAD3 genomes AF: 0.0000591 AC: 9 AN: 152238 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000577

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.0000247 AC: 2 AN: 81124 AF XY: 0.0000454

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000729

Gnomad NFE exome AF: 0.0000286

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000722 AC: 95 AN: 1315524 Hom.: 0 Cov.: 32 AF XY: 0.0000572 AC XY: 37 AN XY: 646768

African (AFR) AF: 0.00 AC: 0 AN: 25470

American (AMR) AF: 0.00 AC: 0 AN: 16496

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22364

East Asian (EAS) AF: 0.000137 AC: 4 AN: 29100

South Asian (SAS) AF: 0.0000153 AC: 1 AN: 65178

European-Finnish (FIN) AF: 0.0000207 AC: 1 AN: 48252

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5464

European-Non Finnish (NFE) AF: 0.0000830 AC: 87 AN: 1048684

Other (OTH) AF: 0.0000367 AC: 2 AN: 54516

GnomAD4 genome AF: 0.0000591 AC: 9 AN: 152238 Hom.: 0 Cov.: 33 AF XY: 0.0000672 AC XY: 5 AN XY: 74376

African (AFR) AF: 0.0000241 AC: 1 AN: 41468

American (AMR) AF: 0.0000654 AC: 1 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.000577 AC: 3 AN: 5200

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68034

Other (OTH) AF: 0.000478 AC: 1 AN: 2092

Alfa AF: 0.0000764 Hom.: 0

Bravo AF: 0.0000227

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.000259 AC: 1

ExAC AF: 0.0000352 AC: 3

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	17
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0028	T
Eigen	Benign	-0.59
Eigen_PC	Benign	-0.41
FATHMM_MKL	Benign	0.29	N
LIST_S2	Benign	0.58	T
M_CAP	Benign	0.0068	T
MetaRNN	Benign	0.075	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.20	N
PhyloP100		-0.13
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.028
Sift	Benign	0.069	T
Sift4G	Benign	0.094	T
Polyphen		0.045	B
Vest4		0.11
MutPred		0.33		Loss of disorder (P = 0.0072)
MVP		0.17
MPC		0.042
ClinPred		0.11	T
GERP RS		2.4
PromoterAI		-0.054	Neutral
Varity_R		0.061
gMVP		0.28
Mutation Taster		=90/10	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs772446015; hg19: chr16-70680857;