NM_001393494.1:c.241-5C>T

Variant names:

• chr16-70656955-C-T
• rs78909989
• NM_001393494.1:c.241-5C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001393494.1(IL34):​c.241-5C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00185 in 1,602,004 control chromosomes in the GnomAD database, including 43 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0098 (24 hom., cov: 32)
  • Exomes 𝑓: 0.0010 (19 hom.)
• Consequence: IL34 NM_001393494.1 splice_region, intron
• Scores: Splicing: ADA: 0.00002013
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.57
• Publications: 0 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: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 16-70656955-C-T is Benign according to our data. Variant chr16-70656955-C-T is described in ClinVar as Benign. ClinVar VariationId is 770634.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00985 (1499/152202) while in subpopulation AFR AF = 0.0343 (1427/41546). AF 95% confidence interval is 0.0329. There are 24 homozygotes in GnomAd4. There are 683 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 24 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001393494.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL34	NM_001393494.1	MANE Select	c.241-5C>T		splice_region intron	N/A	NP_001380423.1	Q6ZMJ4-1
	IL34	NM_001172772.2		c.241-5C>T		splice_region intron	N/A	NP_001166243.1	Q6ZMJ4-1
	IL34	NM_001393493.1		c.241-5C>T		splice_region intron	N/A	NP_001380422.1	Q6ZMJ4-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL34	ENST00000288098.7	TSL:1 MANE Select	c.241-5C>T		splice_region intron	N/A	ENSP00000288098.2	Q6ZMJ4-1
	IL34	ENST00000566361.1	TSL:1	c.166-5C>T		splice_region intron	N/A	ENSP00000463886.1	J3QQT3
	IL34	ENST00000429149.6	TSL:5	c.241-5C>T		splice_region intron	N/A	ENSP00000397863.2	Q6ZMJ4-1

Frequencies

GnomAD3 genomes AF: 0.00984 AC: 1496 AN: 152084 Hom.: 24 Cov.: 32

Gnomad AFR AF: 0.0344

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00314

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000194

Gnomad SAS AF: 0.000208

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.00624

GnomAD2 exomes AF: 0.00248 AC: 606 AN: 244296 AF XY: 0.00184

Gnomad AFR exome AF: 0.0327

Gnomad AMR exome AF: 0.00175

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000109

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000544

Gnomad OTH exome AF: 0.00117

GnomAD4 exome AF: 0.00101 AC: 1458 AN: 1449802 Hom.: 19 Cov.: 31 AF XY: 0.000864 AC XY: 622 AN XY: 719930

African (AFR) AF: 0.0360 AC: 1196 AN: 33210

American (AMR) AF: 0.00182 AC: 80 AN: 43962

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25534

East Asian (EAS) AF: 0.0000758 AC: 3 AN: 39576

South Asian (SAS) AF: 0.000106 AC: 9 AN: 84862

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53046

Middle Eastern (MID) AF: 0.00146 AC: 6 AN: 4120

European-Non Finnish (NFE) AF: 0.0000335 AC: 37 AN: 1105760

Other (OTH) AF: 0.00213 AC: 127 AN: 59732

GnomAD4 genome AF: 0.00985 AC: 1499 AN: 152202 Hom.: 24 Cov.: 32 AF XY: 0.00918 AC XY: 683 AN XY: 74402

African (AFR) AF: 0.0343 AC: 1427 AN: 41546

American (AMR) AF: 0.00314 AC: 48 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.000195 AC: 1 AN: 5134

South Asian (SAS) AF: 0.000208 AC: 1 AN: 4808

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000118 AC: 8 AN: 68022

Other (OTH) AF: 0.00617 AC: 13 AN: 2106

Alfa AF: 0.00621 Hom.: 3

Bravo AF: 0.0112

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.34
DANN	Benign	0.78
PhyloP100		-2.6
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000020
dbscSNV1_RF	Benign	0.0
SpliceAI score (max)		0.020		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: rs78909989; hg19: chr16-70690858;