10-89363067-T-G

Variant names:

• chr10-89363067-T-G
• rs305375
• ENST00000418257.1:n.774T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000418257.1(IFIT6P):​n.774T>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.61 in 226,380 control chromosomes in the GnomAD database, including 45,235 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 0.63 (32979 hom., cov: 32)
  • Exomes 𝑓: 0.56 (12256 hom.)
• Consequence: IFIT6P ENST00000418257.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.71
• Publications: 0 publications found

Genes affected

IFIT6P (HGNC:38020): (interferon induced protein with tetratricopeptide repeats 6, pseudogene)

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]

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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.918 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IFIT6P		n.89363067T>G		intragenic_variant
LIPA	NM_001440819.1	c.-2+49724A>C		intron_variant	Intron 2 of 10		NP_001427748.1
LIPA	NM_001440820.1	c.-2+49674A>C		intron_variant	Intron 2 of 10		NP_001427749.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IFIT6P	ENST00000418257.1	n.774T>G		non_coding_transcript_exon_variant	Exon 1 of 1	6
LIPA	ENST00000371837.5	c.61+49724A>C		intron_variant	Intron 2 of 8	2		ENSP00000360903.1
IFIT3	ENST00000679438.1	c.-15-6372T>G		intron_variant	Intron 1 of 3			ENSP00000506015.1

Frequencies

GnomAD3 genomes AF: 0.632 AC: 96036 AN: 152008 Hom.: 32928 Cov.: 32

Gnomad AFR AF: 0.888

Gnomad AMI AF: 0.655

Gnomad AMR AF: 0.584

Gnomad ASJ AF: 0.626

Gnomad EAS AF: 0.940

Gnomad SAS AF: 0.588

Gnomad FIN AF: 0.493

Gnomad MID AF: 0.601

Gnomad NFE AF: 0.488

Gnomad OTH AF: 0.629

GnomAD4 exome AF: 0.564 AC: 41857 AN: 74254 Hom.: 12256 Cov.: 0 AF XY: 0.554 AC XY: 23787 AN XY: 42930

African (AFR) AF: 0.900 AC: 1899 AN: 2110

American (AMR) AF: 0.554 AC: 4689 AN: 8470

Ashkenazi Jewish (ASJ) AF: 0.649 AC: 785 AN: 1210

East Asian (EAS) AF: 0.936 AC: 4432 AN: 4736

South Asian (SAS) AF: 0.579 AC: 4032 AN: 6960

European-Finnish (FIN) AF: 0.506 AC: 4752 AN: 9398

Middle Eastern (MID) AF: 0.657 AC: 595 AN: 906

European-Non Finnish (NFE) AF: 0.507 AC: 18957 AN: 37360

Other (OTH) AF: 0.553 AC: 1716 AN: 3104

GnomAD4 genome AF: 0.632 AC: 96137 AN: 152126 Hom.: 32979 Cov.: 32 AF XY: 0.634 AC XY: 47153 AN XY: 74382

African (AFR) AF: 0.888 AC: 36852 AN: 41512

American (AMR) AF: 0.583 AC: 8915 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.626 AC: 2172 AN: 3470

East Asian (EAS) AF: 0.940 AC: 4881 AN: 5190

South Asian (SAS) AF: 0.588 AC: 2830 AN: 4814

European-Finnish (FIN) AF: 0.493 AC: 5212 AN: 10566

Middle Eastern (MID) AF: 0.592 AC: 174 AN: 294

European-Non Finnish (NFE) AF: 0.488 AC: 33172 AN: 67974

Other (OTH) AF: 0.631 AC: 1332 AN: 2112

Alfa AF: 0.408 Hom.: 1144

Bravo AF: 0.648

Asia WGS AF: 0.741 AC: 2571 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.3
DANN	Benign	0.64
PhyloP100		1.7
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs305375; hg19: chr10-91122824;