10-89384219-C-G

Position:

• chr10-89384219-C-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001010987.2(IFIT1B):​c.906C>G​(p.Ile302Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: IFIT1B NM_001010987.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0840

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06790501).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IFIT1B	NM_001010987.2	c.906C>G	p.Ile302Met	missense_variant	2/2	ENST00000371809.3	NP_001010987.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IFIT1B	ENST00000371809.3	c.906C>G	p.Ile302Met	missense_variant	2/2	1	NM_001010987.2	ENSP00000360874.3
LIPA	ENST00000371837.5	c.61+28572G>C		intron_variant		2		ENSP00000360903.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 14, 2024

The c.906C>G (p.I302M) alteration is located in exon 2 (coding exon 2) of the IFIT1B gene. This alteration results from a C to G substitution at nucleotide position 906, causing the isoleucine (I) at amino acid position 302 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.086
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	0.39
DANN	Benign	0.52
DEOGEN2	Benign	0.010	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.0063	N
LIST_S2	Benign	0.76	T
M_CAP	Benign	0.0020	T
MetaRNN	Benign	0.068	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.1	L
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.042
Sift	Benign	0.22	T
Sift4G	Benign	0.22	T
Polyphen		0.36	B
Vest4		0.036
MutPred		0.57		Gain of catalytic residue at I302 (P = 0.026);
MVP		0.37
MPC		0.028
ClinPred		0.45	T
GERP RS		-4.4
Varity_R		0.12
gMVP		0.075

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-91143976; COSMIC: COSV65663565;