rs559198

Variant names:

• chr10-89415405-G-A
• rs559198
• NM_012420.3:c.5+602G>A

Your query was ambiguous. Multiple possible variants found:

• chr10-89415405-G-A
• chr10-89415405-G-C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 0 publications found

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]

LIPA (HGNC:6617): (lipase A, lysosomal acid type) This gene encodes lipase A, the lysosomal acid lipase (also known as cholesterol ester hydrolase). This enzyme functions in the lysosome to catalyze the hydrolysis of cholesteryl esters and triglycerides. Mutations in this gene can result in Wolman disease and cholesteryl ester storage disease. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jan 2014]

LIPA Gene-Disease associations (from GenCC):

• lysosomal acid lipase deficiency

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, Genomics England PanelApp, ClinGen, Myriad Women’s Health, Labcorp Genetics (formerly Invitae)
• cholesteryl ester storage disease

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• Wolman disease

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012420.3. 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
	IFIT5	NM_012420.3	MANE Select	c.5+602G>A		intron	N/A	NP_036552.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IFIT5	ENST00000371795.5	TSL:1 MANE Select	c.5+602G>A		intron	N/A	ENSP00000360860.4
	IFIT5	ENST00000681348.1		c.5+602G>A		intron	N/A	ENSP00000505706.1
	IFIT5	ENST00000681422.1		c.-331+602G>A		intron	N/A	ENSP00000506711.1

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

African (AFR) AF: 0.886 AC: 36825 AN: 41572

American (AMR) AF: 0.491 AC: 7514 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.611 AC: 2120 AN: 3468

East Asian (EAS) AF: 0.847 AC: 4389 AN: 5180

South Asian (SAS) AF: 0.582 AC: 2802 AN: 4818

European-Finnish (FIN) AF: 0.510 AC: 5383 AN: 10564

Middle Eastern (MID) AF: 0.559 AC: 162 AN: 290

European-Non Finnish (NFE) AF: 0.498 AC: 33884 AN: 67984

Other (OTH) AF: 0.617 AC: 1303 AN: 2112

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.90
DANN	Benign	0.63
PhyloP100		-0.47
PromoterAI		0.085	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs559198; hg19: chr10-91175162;