NM_001548.5:c.5+2712C>T

Variant names:

• chr10-89395429-C-T
• rs303216
• NM_001548.5:c.5+2712C>T

Variant summary

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

The NM_001548.5(IFIT1):​c.5+2712C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.174 in 152,150 control chromosomes in the GnomAD database, including 2,936 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 0.17 (2936 hom., cov: 31)
• Consequence: IFIT1 NM_001548.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.111
• Publications: 2 publications found

Genes affected

IFIT1 (HGNC:5407): (interferon induced protein with tetratricopeptide repeats 1) This gene encodes a protein containing tetratricopeptide repeats that was originally identified as induced upon treatment with interferon. The encoded protein may inhibit viral replication and translational initiation. This gene is located in a cluster on chromosome 10 with five other closely related genes. There is a pseudogene for this gene on chromosome 13. Alternatively spliced transcript variants encoding multiple isoforms have been observed. [provided by RefSeq, Aug 2012]

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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.43 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IFIT1	NM_001548.5	c.5+2712C>T		intron_variant	Intron 1 of 1	ENST00000371804.4	NP_001539.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IFIT1	ENST00000371804.4	c.5+2712C>T		intron_variant	Intron 1 of 1	1	NM_001548.5	ENSP00000360869.3
IFIT1	ENST00000546318.2	c.-89+2088C>T		intron_variant	Intron 2 of 2	3		ENSP00000441968.1
LIPA	ENST00000371837.5	c.61+17362G>A		intron_variant	Intron 2 of 8	2		ENSP00000360903.1

Frequencies

GnomAD3 genomes AF: 0.174 AC: 26409 AN: 152028 Hom.: 2935 Cov.: 31

Gnomad AFR AF: 0.0550

Gnomad AMI AF: 0.158

Gnomad AMR AF: 0.237

Gnomad ASJ AF: 0.238

Gnomad EAS AF: 0.446

Gnomad SAS AF: 0.340

Gnomad FIN AF: 0.225

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.188

Gnomad OTH AF: 0.178

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

GnomAD4 genome AF: 0.174 AC: 26418 AN: 152150 Hom.: 2936 Cov.: 31 AF XY: 0.181 AC XY: 13486 AN XY: 74374

African (AFR) AF: 0.0551 AC: 2290 AN: 41540

American (AMR) AF: 0.236 AC: 3611 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.238 AC: 825 AN: 3470

East Asian (EAS) AF: 0.445 AC: 2305 AN: 5174

South Asian (SAS) AF: 0.341 AC: 1647 AN: 4824

European-Finnish (FIN) AF: 0.225 AC: 2376 AN: 10570

Middle Eastern (MID) AF: 0.146 AC: 43 AN: 294

European-Non Finnish (NFE) AF: 0.188 AC: 12800 AN: 67984

Other (OTH) AF: 0.179 AC: 377 AN: 2110

Alfa AF: 0.0836 Hom.: 116

Bravo AF: 0.165

Asia WGS AF: 0.317 AC: 1101 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.3
DANN	Benign	0.56
PhyloP100		-0.11
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: rs303216; hg19: chr10-91155186;