rs559198

chr10-89415405-G-Achr10-89415405-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_012420.3(IFIT5):c.5+602G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.625 in 152,190 control chromosomes in the GnomAD database, including 32,245 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 0.63 (32245 hom., cov: 33)
• Consequence: IFIT5 NM_012420.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.466

Genes affected

IFIT5 (HGNC:13328): (interferon induced protein with tetratricopeptide repeats 5) Enables nucleic acid binding activity. Involved in defense response to virus; negative regulation of viral genome replication; and positive regulation of I-kappaB kinase/NF-kappaB signaling. Located in actin cytoskeleton; apical part of cell; and ruffle membrane. Colocalizes with IkappaB kinase complex. [provided by Alliance of Genome Resources, Apr 2022]

LOC107984251 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.878 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IFIT5	NM_012420.3	c.5+602G>A		intron_variant		ENST00000371795.5
LOC107984251	XR_001747541.2	n.474C>T		non_coding_transcript_exon_variant	2/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IFIT5	ENST00000371795.5	c.5+602G>A		intron_variant		1	NM_012420.3	P1

Frequencies

GnomAD3 genomes AF: 0.625 AC: 95036 AN: 152070 Hom.: 32198 Cov.: 33

Gnomad AFR AF: 0.886

Gnomad AMI AF: 0.823

Gnomad AMR AF: 0.492

Gnomad ASJ AF: 0.611

Gnomad EAS AF: 0.848

Gnomad SAS AF: 0.581

Gnomad FIN AF: 0.510

Gnomad MID AF: 0.574

Gnomad NFE AF: 0.498

Gnomad OTH AF: 0.615

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.625 AC: 95133 AN: 152190 Hom.: 32245 Cov.: 33 AF XY: 0.625 AC XY: 46507 AN XY: 74384

Gnomad4 AFR AF: 0.886

Gnomad4 AMR AF: 0.491

Gnomad4 ASJ AF: 0.611

Gnomad4 EAS AF: 0.847

Gnomad4 SAS AF: 0.582

Gnomad4 FIN AF: 0.510

Gnomad4 NFE AF: 0.498

Gnomad4 OTH AF: 0.617

Alfa AF: 0.360 Hom.: 804

Bravo AF: 0.634

Asia WGS AF: 0.682 AC: 2370 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	0.90
Dann	Benign	0.63

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs559198; hg19: chr10-91175162;