chr10-89330794-T-C

Variant names:

• chr10-89330794-T-C
• rs7897619
• NM_001549.6:c.5+2716T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 8 publications found

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]

LIPA Gene-Disease associations (from GenCC):

• lysosomal acid lipase deficiency

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• lysosomal acid lipase deficiency

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, Myriad Women’s Health, Labcorp Genetics (formerly Invitae), Genomics England PanelApp
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.317 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001549.6. 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
	IFIT3	NM_001549.6	MANE Select	c.5+2716T>C		intron	N/A	NP_001540.2
	LIPA	NM_001440836.1		c.14+11767A>G		intron	N/A	NP_001427765.1
	IFIT3	NM_001289758.2		c.-270+2716T>C		intron	N/A	NP_001276687.1	A0A7P0T7D6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IFIT3	ENST00000371818.9	TSL:1 MANE Select	c.5+2716T>C		intron	N/A	ENSP00000360883.4	O14879
	LIPA	ENST00000487618.5	TSL:1	n.64+11817A>G		intron	N/A
	IFIT3	ENST00000680779.1		c.86+2165T>C		intron	N/A	ENSP00000504949.1	A0A7P0T855

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

African (AFR) AF: 0.322 AC: 13345 AN: 41466

American (AMR) AF: 0.232 AC: 3544 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.254 AC: 881 AN: 3472

East Asian (EAS) AF: 0.231 AC: 1194 AN: 5168

South Asian (SAS) AF: 0.110 AC: 529 AN: 4822

European-Finnish (FIN) AF: 0.184 AC: 1946 AN: 10570

Middle Eastern (MID) AF: 0.211 AC: 62 AN: 294

European-Non Finnish (NFE) AF: 0.229 AC: 15548 AN: 67988

Other (OTH) AF: 0.254 AC: 535 AN: 2110

Alfa AF: 0.238 Hom.: 16648

Bravo AF: 0.259

Asia WGS AF: 0.186 AC: 646 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.1
DANN	Benign	0.50
PhyloP100		-0.027
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: rs7897619; hg19: chr10-91090551;