Variant 16-70656608-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001393494.1(IL34):c.169T>C(p.Tyr57His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00205 in 1,331,086 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0019 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0021 ( 7 hom. )

Consequence

IL34
NM_001393494.1 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.523

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 -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.011613637).

BP6

Variant 16-70656608-T-C is Benign according to our data. Variant chr16-70656608-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 3037658.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL34	NM_001393494.1 linkuse as main transcript	c.169T>C	p.Tyr57His	missense_variant	3/6	ENST00000288098.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL34	ENST00000288098.7 linkuse as main transcript	c.169T>C	p.Tyr57His	missense_variant	3/6	1	NM_001393494.1	P2	Q6ZMJ4-1

Frequencies

GnomAD3 genomes

AF:

0.00185

AC:

282

AN:

152164

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000338

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00144

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00113

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00341

Gnomad OTH

AF:

0.000955

GnomAD3 exomes

AF:

0.00168

AC:

423

AN:

251472

Hom.:

AF XY:

0.00166

AC XY:

226

AN XY:

135918

show subpopulations

Gnomad AFR exome

AF:

0.000246

Gnomad AMR exome

AF:

0.000607

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000924

Gnomad NFE exome

AF:

0.00325

Gnomad OTH exome

AF:

0.00130

GnomAD4 exome

AF:

0.00207

AC:

2441

AN:

1178804

Hom.:

Cov.:

AF XY:

0.00207

AC XY:

1240

AN XY:

600288

show subpopulations

Gnomad4 AFR exome

AF:

0.000250

Gnomad4 AMR exome

AF:

0.000676

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00128

Gnomad4 NFE exome

AF:

0.00264

Gnomad4 OTH exome

AF:

0.00161

GnomAD4 genome

AF:

0.00185

AC:

282

AN:

152282

Hom.:

Cov.:

AF XY:

0.00160

AC XY:

119

AN XY:

74456

show subpopulations

Gnomad4 AFR

AF:

0.000337

Gnomad4 AMR

AF:

0.00144

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00113

Gnomad4 NFE

AF:

0.00341

Gnomad4 OTH

AF:

0.000945

Alfa

AF:

0.00274

Hom.:

Bravo

AF:

0.00181

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.00234

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00337

AC:

ExAC

AF:

0.00170

AC:

206

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

IL34-related disorder

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 01, 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

Pathogenic

0.61

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.25

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.059

T;T;T

Eigen

Uncertain

0.32

Eigen_PC

Uncertain

0.29

FATHMM_MKL

Benign

0.75

LIST_S2

Benign

0.81

T;.;T

M_CAP

Benign

0.055

MetaRNN

Benign

0.012

T;T;T

MetaSVM

Benign

-0.60

MutationAssessor

Benign

1.8

L;L;.

MutationTaster

Benign

0.73

D;D;N

PrimateAI

Uncertain

0.57

PROVEAN

Uncertain

-2.4

N;N;.

REVEL

Benign

0.27

Sift

Benign

0.17

T;T;.

Sift4G

Uncertain

0.038

D;D;D

Polyphen

0.99

D;D;.

Vest4

0.40

MVP

0.59

MPC

0.29

ClinPred

0.042

GERP RS

4.3

Varity_R

0.43

gMVP

0.51

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