Variant 16-70659677-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_001393494.1(IL34):c.462A>G(p.Pro154=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00524 in 1,613,110 control chromosomes in the GnomAD database, including 78 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.012 ( 17 hom., cov: 33)

Exomes 𝑓: 0.0045 ( 61 hom. )

Consequence

IL34
NM_001393494.1 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.0330

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 16-70659677-A-G is Benign according to our data. Variant chr16-70659677-A-G is described in ClinVar as [Benign]. Clinvar id is 714712.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.033 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0124 (1892/152320) while in subpopulation AFR AF= 0.0317 (1317/41576). AF 95% confidence interval is 0.0303. There are 17 homozygotes in gnomad4. There are 913 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 17 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL34	NM_001393494.1 linkuse as main transcript	c.462A>G	p.Pro154=	synonymous_variant	5/6	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.462A>G	p.Pro154=	synonymous_variant	5/6	1	NM_001393494.1	ENSP00000288098	P2	Q6ZMJ4-1
IL34	ENST00000566361.1 linkuse as main transcript	c.387A>G	p.Pro129=	synonymous_variant	5/6	1		ENSP00000463886	A2
IL34	ENST00000429149.6 linkuse as main transcript	c.462A>G	p.Pro154=	synonymous_variant	6/7	5		ENSP00000397863	P2	Q6ZMJ4-1

Frequencies

GnomAD3 genomes

AF:

0.0123

AC:

1875

AN:

152202

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0313

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00955

Gnomad ASJ

AF:

0.0409

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00393

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.00326

Gnomad OTH

AF:

0.0163

GnomAD3 exomes

AF:

0.00686

AC:

1718

AN:

250318

Hom.:

AF XY:

0.00633

AC XY:

857

AN XY:

135342

show subpopulations

Gnomad AFR exome

AF:

0.0332

Gnomad AMR exome

AF:

0.00560

Gnomad ASJ exome

AF:

0.0430

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.00318

Gnomad FIN exome

AF:

0.000326

Gnomad NFE exome

AF:

0.00343

Gnomad OTH exome

AF:

0.0103

GnomAD4 exome

AF:

0.00449

AC:

6555

AN:

1460790

Hom.:

Cov.:

AF XY:

0.00449

AC XY:

3264

AN XY:

726680

show subpopulations

Gnomad4 AFR exome

AF:

0.0356

Gnomad4 AMR exome

AF:

0.00647

Gnomad4 ASJ exome

AF:

0.0418

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.00406

Gnomad4 FIN exome

AF:

0.000487

Gnomad4 NFE exome

AF:

0.00257

Gnomad4 OTH exome

AF:

0.00990

GnomAD4 genome

AF:

0.0124

AC:

1892

AN:

152320

Hom.:

Cov.:

AF XY:

0.0123

AC XY:

913

AN XY:

74494

show subpopulations

Gnomad4 AFR

AF:

0.0317

Gnomad4 AMR

AF:

0.00954

Gnomad4 ASJ

AF:

0.0409

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00414

Gnomad4 FIN

AF:

0.000188

Gnomad4 NFE

AF:

0.00326

Gnomad4 OTH

AF:

0.0161

Alfa

AF:

0.00916

Hom.:

Bravo

AF:

0.0139

Asia WGS

AF:

0.0130

AC:

AN:

3478

EpiCase

AF:

0.00436

EpiControl

AF:

0.00523

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jun 14, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

1.6

DANN

Benign

0.64

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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