rs3813905

chr16-70646947-C-Gchr16-70646947-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.60

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
IL34	NM_001393494.1	c.-1C>G		5_prime_UTR_variant	1/6	ENST00000288098.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL34	ENST00000288098.7	c.-1C>G		5_prime_UTR_variant	1/6	1	NM_001393494.1	P2
IL34	ENST00000429149.6	c.-1C>G		5_prime_UTR_variant	2/7	5		P2
IL34	ENST00000569641.1	n.385C>G		non_coding_transcript_exon_variant	1/2	3
IL34	ENST00000574181.1	n.75C>G		non_coding_transcript_exon_variant	1/3	4

Frequencies

GnomAD3 genomes AF: 0.293 AC: 44569 AN: 152078 Hom.: 6783 Cov.: 33

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

GnomAD3 exomes AF: 0.328 AC: 27989 AN: 85374 Hom.: 4983 AF XY: 0.343 AC XY: 15897 AN XY: 46358

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 SAS exome AF: 0.458

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.: 34 AF XY: 0.344 AC XY: 223016 AN XY: 648604

Gnomad4 AFR exome AF: 0.234

Gnomad4 AMR exome AF: 0.199

Gnomad4 ASJ exome AF: 0.386

Gnomad4 EAS exome AF: 0.263

Gnomad4 SAS exome AF: 0.460

Gnomad4 FIN exome AF: 0.272

Gnomad4 NFE exome AF: 0.342

Gnomad4 OTH exome AF: 0.341

GnomAD4 genome AF: 0.293 AC: 44615 AN: 152194 Hom.: 6796 Cov.: 33 AF XY: 0.293 AC XY: 21760 AN XY: 74392

Gnomad4 AFR AF: 0.230

Gnomad4 AMR AF: 0.232

Gnomad4 ASJ AF: 0.380

Gnomad4 EAS AF: 0.278

Gnomad4 SAS AF: 0.453

Gnomad4 FIN AF: 0.267

Gnomad4 NFE AF: 0.335

Gnomad4 OTH AF: 0.303

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	20
Dann	Benign	0.92

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

Other links and lift over

dbSNP: rs3813905; hg19: chr16-70680850; COSMIC: COSV55379873;