Genetic Variant IL34:c.-1C>G (chr16-70646947-C-G) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_ModerateBA1

The NM_001393494.1(IL34):c.-1C>G variant causes a 5 prime UTR change. The variant allele was found at a frequency of 0.335 in 1,470,958 control chromosomes in the GnomAD database, including 85,092 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.29 ( 6796 hom., cov: 33)

Exomes 𝑓: 0.34 ( 78296 hom. )

Consequence

IL34
NM_001393494.1 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.60

Publications

11 publications found

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 was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.32).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.438 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL34	NM_001393494.1 link	c.-1C>G		5_prime_UTR_variant	Exon 1 of 6	ENST00000288098.7	NP_001380423.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
IL34	ENST00000288098.7 link	c.-1C>G	5_prime_UTR_variant	Exon 1 of 6	1	NM_001393494.1	ENSP00000288098.2	Q6ZMJ4-1
IL34	ENST00000569641.1 link	n.385C>G	non_coding_transcript_exon_variant	Exon 1 of 2	3
IL34	ENST00000574181.1 link	n.75C>G	non_coding_transcript_exon_variant	Exon 1 of 3	4
IL34	ENST00000429149.6 link	c.-1C>G	5_prime_UTR_variant	Exon 2 of 7	5		ENSP00000397863.2	Q6ZMJ4-1

Frequencies

GnomAD3 genomes

AF:

0.293

AC:

44569

AN:

152078

Hom.:

6783

Cov.:

show subpopulations

Gnomad AFR

AF:

0.230

Gnomad AMI

AF:

0.280

Gnomad AMR

AF:

0.232

Gnomad ASJ

AF:

0.380

Gnomad EAS

AF:

0.278

Gnomad SAS

AF:

0.452

Gnomad FIN

AF:

0.267

Gnomad MID

AF:

0.345

Gnomad NFE

AF:

0.335

Gnomad OTH

AF:

0.296

GnomAD2 exomes

AF:

0.328

AC:

27989

AN:

85374

AF XY:

0.343

show subpopulations

Gnomad AFR exome

AF:

0.226

Gnomad AMR exome

AF:

0.190

Gnomad ASJ exome

AF:

0.397

Gnomad EAS exome

AF:

0.268

Gnomad FIN exome

AF:

0.264

Gnomad NFE exome

AF:

0.337

Gnomad OTH exome

AF:

0.319

GnomAD4 exome

AF:

0.340

AC:

448582

AN:

1318764

Hom.:

78296

Cov.:

AF XY:

0.344

AC XY:

223016

AN XY:

648604

show subpopulations

African (AFR)

AF:

0.234

AC:

6043

AN:

25796

American (AMR)

AF:

0.199

AC:

3561

AN:

17852

Ashkenazi Jewish (ASJ)

AF:

0.386

AC:

8713

AN:

22596

East Asian (EAS)

AF:

0.263

AC:

7661

AN:

29160

South Asian (SAS)

AF:

0.460

AC:

30415

AN:

66104

European-Finnish (FIN)

AF:

0.272

AC:

13095

AN:

48186

Middle Eastern (MID)

AF:

0.391

AC:

2139

AN:

5470

European-Non Finnish (NFE)

AF:

0.342

AC:

358300

AN:

1048938

Other (OTH)

AF:

0.341

AC:

18655

AN:

54662

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.459

Heterozygous variant carriers

14217

28434

42650

56867

71084

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

11916

23832

35748

47664

59580

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.293

AC:

44615

AN:

152194

Hom.:

6796

Cov.:

AF XY:

0.293

AC XY:

21760

AN XY:

74392

show subpopulations

African (AFR)

AF:

0.230

AC:

9548

AN:

41550

American (AMR)

AF:

0.232

AC:

3542

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.380

AC:

1318

AN:

3466

East Asian (EAS)

AF:

0.278

AC:

1439

AN:

5170

South Asian (SAS)

AF:

0.453

AC:

2186

AN:

4822

European-Finnish (FIN)

AF:

0.267

AC:

2828

AN:

10592

Middle Eastern (MID)

AF:

0.350

AC:

103

AN:

294

European-Non Finnish (NFE)

AF:

0.335

AC:

22755

AN:

67996

Other (OTH)

AF:

0.303

AC:

641

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1645

3290

4935

6580

8225

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

464

928

1392

1856

2320

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.325

Hom.:

2685

Bravo

AF:

0.287

Asia WGS

AF:

0.387

AC:

1347

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.32

CADD

Benign

(source)

DANN

Benign

0.92

PhyloP100

3.6

PromoterAI

-0.025

Neutral

(source)

Mutation Taster

=284/16

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over