rs4630205

Positions:

• chr10-89332949-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+4871T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.323 in 152,050 control chromosomes in the GnomAD database, including 9,083 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 0.32 (9083 hom., cov: 32)
• Consequence: IFIT3 NM_001549.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.40

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]

LOC101926887 (HGNC:):

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.496 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IFIT3	NM_001549.6	c.5+4871T>C		intron_variant		ENST00000371818.9	NP_001540.2
LOC101926887	XR_946183.4	n.2806A>G		non_coding_transcript_exon_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IFIT3	ENST00000371818.9	c.5+4871T>C		intron_variant		1	NM_001549.6	ENSP00000360883	P2

Frequencies

GnomAD3 genomes AF: 0.323 AC: 49046 AN: 151932 Hom.: 9076 Cov.: 32

Gnomad AFR AF: 0.502

Gnomad AMI AF: 0.454

Gnomad AMR AF: 0.280

Gnomad ASJ AF: 0.330

Gnomad EAS AF: 0.324

Gnomad SAS AF: 0.123

Gnomad FIN AF: 0.201

Gnomad MID AF: 0.307

Gnomad NFE AF: 0.255

Gnomad OTH AF: 0.318

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

GnomAD4 genome AF: 0.323 AC: 49083 AN: 152050 Hom.: 9083 Cov.: 32 AF XY: 0.317 AC XY: 23582 AN XY: 74342

Gnomad4 AFR AF: 0.502

Gnomad4 AMR AF: 0.279

Gnomad4 ASJ AF: 0.330

Gnomad4 EAS AF: 0.324

Gnomad4 SAS AF: 0.122

Gnomad4 FIN AF: 0.201

Gnomad4 NFE AF: 0.255

Gnomad4 OTH AF: 0.317

Alfa AF: 0.292 Hom.: 1204

Bravo AF: 0.341

Asia WGS AF: 0.247 AC: 857 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.6
DANN	Benign	0.44

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: rs4630205; hg19: chr10-91092706;