dbSNP rs10509571: IFIT3:c.5+4723T>A (chr10-89332801-T-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001549.6(IFIT3):c.5+4723T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.266 in 152,014 control chromosomes in the GnomAD database, including 5,717 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 0.27 ( 5717 hom., cov: 32)

Consequence

IFIT3
NM_001549.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.397

Publications

4 publications found

Variant links:

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]

IFIT3 links:

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

LIPA links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.75).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.32 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IFIT3	NM_001549.6 link	c.5+4723T>A		intron_variant	Intron 1 of 1	ENST00000371818.9	NP_001540.2	O14879Q5T765

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IFIT3	ENST00000371818.9 link	c.5+4723T>A		intron_variant	Intron 1 of 1	1	NM_001549.6	ENSP00000360883.4		O14879

Frequencies

GnomAD3 genomes

AF:

0.267

AC:

40486

AN:

151896

Hom.:

5719

Cov.:

show subpopulations

Gnomad AFR

AF:

0.325

Gnomad AMI

AF:

0.449

Gnomad AMR

AF:

0.251

Gnomad ASJ

AF:

0.314

Gnomad EAS

AF:

0.324

Gnomad SAS

AF:

0.123

Gnomad FIN

AF:

0.199

Gnomad MID

AF:

0.285

Gnomad NFE

AF:

0.246

Gnomad OTH

AF:

0.274

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

GnomAD4 genome

AF:

0.266

AC:

40505

AN:

152014

Hom.:

5717

Cov.:

AF XY:

0.263

AC XY:

19538

AN XY:

74306

show subpopulations

African (AFR)

AF:

0.325

AC:

13459

AN:

41430

American (AMR)

AF:

0.251

AC:

3830

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.314

AC:

1090

AN:

3472

East Asian (EAS)

AF:

0.324

AC:

1674

AN:

5164

South Asian (SAS)

AF:

0.121

AC:

586

AN:

4826

European-Finnish (FIN)

AF:

0.199

AC:

2101

AN:

10550

Middle Eastern (MID)

AF:

0.269

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.246

AC:

16700

AN:

67980

Other (OTH)

AF:

0.273

AC:

577

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1540

3079

4619

6158

7698

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.249

Hom.:

628

Bravo

AF:

0.277

Asia WGS

AF:

0.236

AC:

818

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.75

CADD

Benign

6.7

(source)

DANN

Benign

0.82

PhyloP100

-0.40

PromoterAI

0.00070

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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rs10509571

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over