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]

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IFI35	NM_001330230.2	c.562+55C>T		intron_variant	Intron 5 of 6	ENST00000415816.7	NP_001317159.1
IFI35	NM_005533.5	c.568+55C>T		intron_variant	Intron 5 of 6		NP_005524.2
IFI35	XM_017024584.2	c.508+55C>T		intron_variant	Intron 5 of 6		XP_016880073.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IFI35	ENST00000415816.7	c.562+55C>T		intron_variant	Intron 5 of 6	5	NM_001330230.2	ENSP00000394579.3

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 v4.3

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;