16-70646947-C-T

Variant names:

• chr16-70646947-C-T
• rs3813905
• NM_001393494.1:c.-1C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001393494.1(IL34):​c.-1C>T variant causes a 5 prime UTR change. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: IL34 NM_001393494.1 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.60
• Publications: 11 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.29).

Transcripts

RefSeq

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

Ensembl

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

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1319822 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 649080

African (AFR) AF: 0.00 AC: 0 AN: 25810

American (AMR) AF: 0.00 AC: 0 AN: 17880

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22606

East Asian (EAS) AF: 0.00 AC: 0 AN: 29166

South Asian (SAS) AF: 0.00 AC: 0 AN: 66192

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48230

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5472

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1049760

Other (OTH) AF: 0.00 AC: 0 AN: 54706

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.29
CADD	Benign	20
DANN	Benign	0.93
PhyloP100		3.6
PromoterAI		-0.13	Neutral

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs3813905; hg19: chr16-70680850;