rs4630205

Variant names:

• chr10-89332949-T-C
• rs4630205
• NM_001549.6:c.5+4871T>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+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
• Publications: 6 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.496 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+4871T>C		intron	N/A	NP_001540.2
	IFIT3	NM_001031683.4		c.5+322T>C		intron	N/A	NP_001026853.1	Q5T765
	LIPA	NM_001440836.1		c.14+9612A>G		intron	N/A	NP_001427765.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IFIT3	ENST00000371818.9	TSL:1 MANE Select	c.5+4871T>C		intron	N/A	ENSP00000360883.4	O14879
	IFIT3	ENST00000371811.4	TSL:1	c.5+322T>C		intron	N/A	ENSP00000360876.4	O14879
	LIPA	ENST00000487618.5	TSL:1	n.64+9662A>G		intron	N/A

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

African (AFR) AF: 0.502 AC: 20777 AN: 41426

American (AMR) AF: 0.279 AC: 4269 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.330 AC: 1143 AN: 3468

East Asian (EAS) AF: 0.324 AC: 1670 AN: 5162

South Asian (SAS) AF: 0.122 AC: 588 AN: 4814

European-Finnish (FIN) AF: 0.201 AC: 2130 AN: 10600

Middle Eastern (MID) AF: 0.296 AC: 87 AN: 294

European-Non Finnish (NFE) AF: 0.255 AC: 17334 AN: 67974

Other (OTH) AF: 0.317 AC: 671 AN: 2114

Alfa AF: 0.299 Hom.: 1316

Bravo AF: 0.341

Asia WGS AF: 0.247 AC: 857 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.6
DANN	Benign	0.44
PhyloP100		-1.4
PromoterAI		-0.034	Neutral
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: rs4630205; hg19: chr10-91092706;