chr17-43013717-C-T

Variant names:

• chr17-43013717-C-T
• rs443759
• NM_001330230.2:c.562+55C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001330230.2(IFI35):​c.562+55C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.791 in 1,609,464 control chromosomes in the GnomAD database, including 505,437 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 0.75 (43007 hom., cov: 30)
  • Exomes 𝑓: 0.80 (462430 hom.)
• Consequence: IFI35 NM_001330230.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.77
• Publications: 20 publications found

Genes affected

IFI35 (HGNC:5399): (interferon induced protein 35) Enables identical protein binding activity. Involved in several processes, including macrophage activation involved in immune response; positive regulation of defense response; and regulation of signal transduction. Located in several cellular components, including cytosol; extracellular space; and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

VAT1 (HGNC:16919): (vesicle amine transport 1) Synaptic vesicles are responsible for regulating the storage and release of neurotransmitters in the nerve terminal. The protein encoded by this gene is an abundant integral membrane protein of cholinergic synaptic vesicles and is thought to be involved in vesicular transport. It belongs to the quinone oxidoreductase subfamily of zinc-containing alcohol dehydrogenase proteins. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.896 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001330230.2. 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
	IFI35	NM_001330230.2	MANE Select	c.562+55C>T		intron	N/A	NP_001317159.1	P80217-1
	IFI35	NM_005533.5		c.568+55C>T		intron	N/A	NP_005524.2	P80217-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IFI35	ENST00000415816.7	TSL:5 MANE Select	c.562+55C>T		intron	N/A	ENSP00000394579.3	P80217-1
	IFI35	ENST00000438323.2	TSL:1	c.568+55C>T		intron	N/A	ENSP00000395590.2	P80217-2
	VAT1	ENST00000943217.1		c.*1+2343G>A		intron	N/A	ENSP00000613276.1

Frequencies

GnomAD3 genomes AF: 0.748 AC: 113494 AN: 151724 Hom.: 42976 Cov.: 30

Gnomad AFR AF: 0.627

Gnomad AMI AF: 0.743

Gnomad AMR AF: 0.818

Gnomad ASJ AF: 0.796

Gnomad EAS AF: 0.917

Gnomad SAS AF: 0.739

Gnomad FIN AF: 0.730

Gnomad MID AF: 0.794

Gnomad NFE AF: 0.793

Gnomad OTH AF: 0.773

GnomAD4 exome AF: 0.795 AC: 1159192 AN: 1457622 Hom.: 462430 Cov.: 34 AF XY: 0.793 AC XY: 575399 AN XY: 725300

African (AFR) AF: 0.632 AC: 21103 AN: 33394

American (AMR) AF: 0.866 AC: 38694 AN: 44674

Ashkenazi Jewish (ASJ) AF: 0.799 AC: 20822 AN: 26070

East Asian (EAS) AF: 0.927 AC: 36790 AN: 39678

South Asian (SAS) AF: 0.731 AC: 63014 AN: 86186

European-Finnish (FIN) AF: 0.738 AC: 39311 AN: 53234

Middle Eastern (MID) AF: 0.792 AC: 4559 AN: 5758

European-Non Finnish (NFE) AF: 0.800 AC: 886957 AN: 1108390

Other (OTH) AF: 0.796 AC: 47942 AN: 60238

GnomAD4 genome AF: 0.748 AC: 113576 AN: 151842 Hom.: 43007 Cov.: 30 AF XY: 0.748 AC XY: 55493 AN XY: 74174

African (AFR) AF: 0.628 AC: 25970 AN: 41364

American (AMR) AF: 0.818 AC: 12491 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.796 AC: 2759 AN: 3468

East Asian (EAS) AF: 0.918 AC: 4713 AN: 5134

South Asian (SAS) AF: 0.738 AC: 3555 AN: 4814

European-Finnish (FIN) AF: 0.730 AC: 7705 AN: 10562

Middle Eastern (MID) AF: 0.786 AC: 231 AN: 294

European-Non Finnish (NFE) AF: 0.793 AC: 53856 AN: 67922

Other (OTH) AF: 0.768 AC: 1618 AN: 2108

Alfa AF: 0.780 Hom.: 114974

Bravo AF: 0.755

Asia WGS AF: 0.781 AC: 2716 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.9
DANN	Benign	0.84
PhyloP100		-1.8
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs443759; hg19: chr17-41165734;