Variant chr16-70660153-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP6

The NM_001393494.1(IL34):c.695C>T(p.Pro232Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000233 in 1,606,494 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.0011 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00014 ( 0 hom. )

Consequence

IL34
NM_001393494.1 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: -2.08

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.004100263).

BP6

Variant 16-70660153-C-T is Benign according to our data. Variant chr16-70660153-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3037865.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL34	NM_001393494.1 linkuse as main transcript	c.695C>T	p.Pro232Leu	missense_variant	6/6	ENST00000288098.7	NP_001380423.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL34	ENST00000288098.7 linkuse as main transcript	c.695C>T	p.Pro232Leu	missense_variant	6/6	1	NM_001393494.1	ENSP00000288098	P2	Q6ZMJ4-1
IL34	ENST00000566361.1 linkuse as main transcript	c.620C>T	p.Pro207Leu	missense_variant	6/6	1		ENSP00000463886	A2
IL34	ENST00000429149.6 linkuse as main transcript	c.695C>T	p.Pro232Leu	missense_variant	7/7	5		ENSP00000397863	P2	Q6ZMJ4-1

Frequencies

GnomAD3 genomes

AF:

0.00109

AC:

166

AN:

152122

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00377

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000458

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000294

AC:

AN:

238226

Hom.:

AF XY:

0.000216

AC XY:

AN XY:

129496

show subpopulations

Gnomad AFR exome

AF:

0.00333

Gnomad AMR exome

AF:

0.000212

Gnomad ASJ exome

AF:

0.000323

Gnomad EAS exome

AF:

0.0000563

Gnomad SAS exome

AF:

0.0000689

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000375

Gnomad OTH exome

AF:

0.000344

GnomAD4 exome

AF:

0.000143

AC:

208

AN:

1454254

Hom.:

Cov.:

AF XY:

0.000126

AC XY:

AN XY:

723250

show subpopulations

Gnomad4 AFR exome

AF:

0.00371

Gnomad4 AMR exome

AF:

0.000185

Gnomad4 ASJ exome

AF:

0.000195

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.0000353

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000451

Gnomad4 OTH exome

AF:

0.000216

GnomAD4 genome

AF:

0.00110

AC:

167

AN:

152240

Hom.:

Cov.:

AF XY:

0.000954

AC XY:

AN XY:

74440

show subpopulations

Gnomad4 AFR

AF:

0.00378

Gnomad4 AMR

AF:

0.000458

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.000194

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000216

Hom.:

Bravo

AF:

0.00117

ESP6500AA

AF:

0.00319

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000387

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

IL34-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 09, 2022

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.080

BayesDel_addAF

Benign

-0.67

BayesDel_noAF

Benign

-0.74

CADD

Benign

0.26

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0019

T;T;T

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.010

LIST_S2

Benign

0.48

T;.;T

M_CAP

Benign

0.0051

MetaRNN

Benign

0.0041

T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.76

N;N;.

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.29

PROVEAN

Benign

-0.50

N;N;.

REVEL

Benign

0.013

Sift

Uncertain

0.028

D;D;.

Sift4G

Benign

0.28

T;T;T

Polyphen

0.0010

B;B;.

Vest4

0.026

MVP

0.13

MPC

0.041

ClinPred

0.0087

GERP RS

-2.4

Varity_R

0.026

gMVP

0.15

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over