rs12781453

Positions:

• chr10-89381112-G-A

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
IFIT1B	NM_001010987.2	c.6-2207G>A		intron_variant		ENST00000371809.3	NP_001010987.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IFIT1B	ENST00000371809.3	c.6-2207G>A		intron_variant		1	NM_001010987.2	ENSP00000360874.3
LIPA	ENST00000371837.5	c.61+31679C>T		intron_variant		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

Gnomad4 AFR AF: 0.261

Gnomad4 AMR AF: 0.248

Gnomad4 ASJ AF: 0.284

Gnomad4 EAS AF: 0.239

Gnomad4 SAS AF: 0.117

Gnomad4 FIN AF: 0.210

Gnomad4 NFE AF: 0.258

Gnomad4 OTH AF: 0.267

Alfa AF: 0.247 Hom.: 609

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs12781453; hg19: chr10-91140869;