rs12781453

Variant names:

• chr10-89381112-G-A
• rs12781453
• NM_001010987.2:c.6-2207G>A

Variant summary

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

The NM_001010987.2(IFIT1B):​c.6-2207G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.251 in 152,034 control chromosomes in the GnomAD database, including 5,028 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 0.25 (5028 hom., cov: 31)
• Consequence: IFIT1B NM_001010987.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.654
• Publications: 1 publications found

Genes affected

IFIT1B (HGNC:23442): (interferon induced protein with tetratricopeptide repeats 1B) Predicted to enable RNA binding activity. Predicted to be involved in defense response to virus. Predicted to act upstream of or within cellular response to interferon-alpha; cellular response to interferon-beta; and response to bacterium. Predicted to be located in cytoplasm. Predicted to be active in cytosol. [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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.257 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IFIT1B	NM_001010987.2	c.6-2207G>A		intron_variant	Intron 1 of 1	ENST00000371809.3	NP_001010987.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IFIT1B	ENST00000371809.3	c.6-2207G>A		intron_variant	Intron 1 of 1	1	NM_001010987.2	ENSP00000360874.3
LIPA	ENST00000371837.5	c.61+31679C>T		intron_variant	Intron 2 of 8	2		ENSP00000360903.1

Frequencies

GnomAD3 genomes AF: 0.251 AC: 38205 AN: 151916 Hom.: 5030 Cov.: 31

Gnomad AFR AF: 0.261

Gnomad AMI AF: 0.443

Gnomad AMR AF: 0.249

Gnomad ASJ AF: 0.284

Gnomad EAS AF: 0.239

Gnomad SAS AF: 0.118

Gnomad FIN AF: 0.210

Gnomad MID AF: 0.294

Gnomad NFE AF: 0.258

Gnomad OTH AF: 0.267

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

GnomAD4 genome AF: 0.251 AC: 38216 AN: 152034 Hom.: 5028 Cov.: 31 AF XY: 0.248 AC XY: 18412 AN XY: 74312

African (AFR) AF: 0.261 AC: 10835 AN: 41452

American (AMR) AF: 0.248 AC: 3795 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.284 AC: 985 AN: 3468

East Asian (EAS) AF: 0.239 AC: 1235 AN: 5172

South Asian (SAS) AF: 0.117 AC: 562 AN: 4818

European-Finnish (FIN) AF: 0.210 AC: 2220 AN: 10576

Middle Eastern (MID) AF: 0.289 AC: 85 AN: 294

European-Non Finnish (NFE) AF: 0.258 AC: 17533 AN: 67952

Other (OTH) AF: 0.267 AC: 562 AN: 2108

Alfa AF: 0.248 Hom.: 640

Bravo AF: 0.260

Asia WGS AF: 0.182 AC: 631 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	9.6
DANN	Benign	0.37
PhyloP100		0.65
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: rs12781453; hg19: chr10-91140869;