Variant 16-70654556-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_001393494.1(IL34):c.47G>C(p.Gly16Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00182 in 1,612,670 control chromosomes in the GnomAD database, including 3 homozygotes. 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 (★★).

Frequency

Genomes: 𝑓 0.0013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0019 ( 3 hom. )

Consequence

IL34
NM_001393494.1 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.13

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 Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0053960383).

BP6

Variant 16-70654556-G-C is Benign according to our data. Variant chr16-70654556-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 733439.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL34	NM_001393494.1 linkuse as main transcript	c.47G>C	p.Gly16Ala	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 linkuse as main transcript	c.47G>C	p.Gly16Ala	missense_variant	2/6	1	NM_001393494.1	ENSP00000288098	P2	Q6ZMJ4-1

Frequencies

GnomAD3 genomes

AF:

0.00129

AC:

196

AN:

152210

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000482

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000851

Gnomad ASJ

AF:

0.00835

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00195

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00126

AC:

316

AN:

250386

Hom.:

AF XY:

0.00115

AC XY:

156

AN XY:

135278

show subpopulations

Gnomad AFR exome

AF:

0.000185

Gnomad AMR exome

AF:

0.000291

Gnomad ASJ exome

AF:

0.00857

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000277

Gnomad NFE exome

AF:

0.00183

Gnomad OTH exome

AF:

0.000654

GnomAD4 exome

AF:

0.00187

AC:

2734

AN:

1460342

Hom.:

Cov.:

AF XY:

0.00185

AC XY:

1347

AN XY:

726248

show subpopulations

Gnomad4 AFR exome

AF:

0.0000896

Gnomad4 AMR exome

AF:

0.000381

Gnomad4 ASJ exome

AF:

0.00801

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000187

Gnomad4 NFE exome

AF:

0.00215

Gnomad4 OTH exome

AF:

0.00177

GnomAD4 genome

AF:

0.00129

AC:

196

AN:

152328

Hom.:

Cov.:

AF XY:

0.00129

AC XY:

AN XY:

74484

show subpopulations

Gnomad4 AFR

AF:

0.000481

Gnomad4 AMR

AF:

0.000850

Gnomad4 ASJ

AF:

0.00835

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000942

Gnomad4 NFE

AF:

0.00196

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00236

Hom.:

Bravo

AF:

0.00117

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.00389

AC:

ESP6500AA

AF:

0.000455

AC:

ESP6500EA

AF:

0.00244

AC:

ExAC

AF:

0.000972

AC:

118

EpiCase

AF:

0.00169

EpiControl

AF:

0.00220

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Apr 10, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.52

CADD

Benign

DANN

Benign

0.88

DEOGEN2

Benign

0.088

T;.;T

Eigen

Benign

-0.42

Eigen_PC

Benign

-0.42

FATHMM_MKL

Benign

0.55

LIST_S2

Benign

0.64

T;T;.

M_CAP

Benign

0.025

MetaRNN

Benign

0.0054

T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

1.5

L;.;L

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.42

PROVEAN

Uncertain

-4.1

D;D;D

REVEL

Benign

0.030

Sift

Uncertain

0.017

D;D;D

Sift4G

Uncertain

0.031

D;D;D

Polyphen

0.13

B;.;B

Vest4

0.30

MVP

0.39

MPC

0.062

ClinPred

0.031

GERP RS

2.9

Varity_R

0.14

gMVP

0.42

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