10-89402740-A-G

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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

GnomAD3 exomes AF: 0.960 AC: 241411 AN: 251354 Hom.: 116022 AF XY: 0.960 AC XY: 130426 AN XY: 135840

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 SAS exome AF: 0.985

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

Gnomad4 AFR exome AF: 0.992

Gnomad4 AMR exome AF: 0.970

Gnomad4 ASJ exome AF: 0.944

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 0.984

Gnomad4 FIN exome AF: 0.931

Gnomad4 NFE exome AF: 0.947

Gnomad4 OTH exome AF: 0.953

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

Gnomad4 AFR AF: 0.991

Gnomad4 AMR AF: 0.958

Gnomad4 ASJ AF: 0.947

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 0.982

Gnomad4 FIN AF: 0.931

Gnomad4 NFE AF: 0.948

Gnomad4 OTH AF: 0.956

Alfa AF: 0.952 Hom.: 101251

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

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: rs303211; hg19: chr10-91162497; COSMIC: COSV65661485;