10-89402740-A-G

Variant names:

• chr10-89402740-A-G
• rs303211
• NM_001548.5:c.465A>G

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001548.5(IFIT1):​c.465A>G​(p.Lys155Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.953 in 1,614,220 control chromosomes in the GnomAD database, including 733,546 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 0.96 (70626 hom., cov: 32)
  • Exomes 𝑓: 0.95 (662920 hom.)
• Consequence: IFIT1 NM_001548.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.530
• Publications: 21 publications found

Genes affected

IFIT1 (HGNC:5407): (interferon induced protein with tetratricopeptide repeats 1) This gene encodes a protein containing tetratricopeptide repeats that was originally identified as induced upon treatment with interferon. The encoded protein may inhibit viral replication and translational initiation. This gene is located in a cluster on chromosome 10 with five other closely related genes. There is a pseudogene for this gene on chromosome 13. Alternatively spliced transcript variants encoding multiple isoforms have been observed. [provided by RefSeq, Aug 2012]

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

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP7: Synonymous conserved (PhyloP=-0.53 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.983 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IFIT1	NM_001548.5	c.465A>G	p.Lys155Lys	synonymous_variant	Exon 2 of 2	ENST00000371804.4	NP_001539.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IFIT1	ENST00000371804.4	c.465A>G	p.Lys155Lys	synonymous_variant	Exon 2 of 2	1	NM_001548.5	ENSP00000360869.3
IFIT1	ENST00000546318.2	c.372A>G	p.Lys124Lys	synonymous_variant	Exon 3 of 3	3		ENSP00000441968.1
LIPA	ENST00000371837.5	c.61+10051T>C		intron_variant	Intron 2 of 8	2		ENSP00000360903.1

Frequencies

GnomAD3 genomes AF: 0.963 AC: 146524 AN: 152216 Hom.: 70567 Cov.: 32

Gnomad AFR AF: 0.991

Gnomad AMI AF: 0.988

Gnomad AMR AF: 0.958

Gnomad ASJ AF: 0.947

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.982

Gnomad FIN AF: 0.931

Gnomad MID AF: 0.959

Gnomad NFE AF: 0.948

Gnomad OTH AF: 0.956

GnomAD2 exomes AF: 0.960 AC: 241411 AN: 251354 AF XY: 0.960

Gnomad AFR exome AF: 0.992

Gnomad AMR exome AF: 0.972

Gnomad ASJ exome AF: 0.946

Gnomad EAS exome AF: 1.00

Gnomad FIN exome AF: 0.931

Gnomad NFE exome AF: 0.947

Gnomad OTH exome AF: 0.954

GnomAD4 exome AF: 0.952 AC: 1392001 AN: 1461886 Hom.: 662920 Cov.: 64 AF XY: 0.953 AC XY: 693069 AN XY: 727246

African (AFR) AF: 0.992 AC: 33227 AN: 33480

American (AMR) AF: 0.970 AC: 43394 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.944 AC: 24674 AN: 26136

East Asian (EAS) AF: 1.00 AC: 39694 AN: 39698

South Asian (SAS) AF: 0.984 AC: 84882 AN: 86256

European-Finnish (FIN) AF: 0.931 AC: 49738 AN: 53420

Middle Eastern (MID) AF: 0.964 AC: 5562 AN: 5768

European-Non Finnish (NFE) AF: 0.947 AC: 1053250 AN: 1112008

Other (OTH) AF: 0.953 AC: 57580 AN: 60396

GnomAD4 genome AF: 0.963 AC: 146642 AN: 152334 Hom.: 70626 Cov.: 32 AF XY: 0.963 AC XY: 71687 AN XY: 74480

African (AFR) AF: 0.991 AC: 41176 AN: 41560

American (AMR) AF: 0.958 AC: 14675 AN: 15312

Ashkenazi Jewish (ASJ) AF: 0.947 AC: 3287 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5188 AN: 5188

South Asian (SAS) AF: 0.982 AC: 4737 AN: 4824

European-Finnish (FIN) AF: 0.931 AC: 9883 AN: 10616

Middle Eastern (MID) AF: 0.956 AC: 281 AN: 294

European-Non Finnish (NFE) AF: 0.948 AC: 64491 AN: 68040

Other (OTH) AF: 0.956 AC: 2023 AN: 2116

Alfa AF: 0.955 Hom.: 132978

Bravo AF: 0.964

Asia WGS AF: 0.993 AC: 3453 AN: 3478

EpiCase AF: 0.946

EpiControl AF: 0.945

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.9
DANN	Benign	0.63
PhyloP100		-0.53
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: rs303211; hg19: chr10-91162497; COSMIC: COSV65661485;