10-89330794-T-C

Position:

• chr10-89330794-T-C

Variant summary

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

The NM_001549.6(IFIT3):​c.5+2716T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.25 in 152,082 control chromosomes in the GnomAD database, including 5,060 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 (5060 hom., cov: 32)
• Consequence: IFIT3 NM_001549.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0270

Genes affected

IFIT3 (HGNC:5411): (interferon induced protein with tetratricopeptide repeats 3) Enables identical protein binding activity. Involved in negative regulation of apoptotic process; negative regulation of cell population proliferation; and response to virus. Located in cytosol and mitochondrion. [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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.317 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IFIT3	NM_001549.6	c.5+2716T>C		intron_variant		ENST00000371818.9	NP_001540.2
IFIT3	NM_001289758.2	c.-270+2716T>C		intron_variant			NP_001276687.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IFIT3	ENST00000371818.9	c.5+2716T>C		intron_variant		1	NM_001549.6	ENSP00000360883	P2

Frequencies

GnomAD3 genomes AF: 0.250 AC: 37925 AN: 151964 Hom.: 5060 Cov.: 32

Gnomad AFR AF: 0.322

Gnomad AMI AF: 0.400

Gnomad AMR AF: 0.232

Gnomad ASJ AF: 0.254

Gnomad EAS AF: 0.231

Gnomad SAS AF: 0.111

Gnomad FIN AF: 0.184

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.229

Gnomad OTH AF: 0.254

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

GnomAD4 genome AF: 0.250 AC: 37949 AN: 152082 Hom.: 5060 Cov.: 32 AF XY: 0.245 AC XY: 18251 AN XY: 74344

Gnomad4 AFR AF: 0.322

Gnomad4 AMR AF: 0.232

Gnomad4 ASJ AF: 0.254

Gnomad4 EAS AF: 0.231

Gnomad4 SAS AF: 0.110

Gnomad4 FIN AF: 0.184

Gnomad4 NFE AF: 0.229

Gnomad4 OTH AF: 0.254

Alfa AF: 0.234 Hom.: 7055

Bravo AF: 0.259

Asia WGS AF: 0.186 AC: 646 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.1
DANN	Benign	0.50

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: rs7897619; hg19: chr10-91090551;