ENST00000418257.1:n.774T>C

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000418257.1(IFIT6P):​n.774T>C 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 0.0000134 in 74,442 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.000013 (0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000418257.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LIPA	NM_001440819.1		c.-2+49724A>G		intron	N/A	NP_001427748.1
	LIPA	NM_001440820.1		c.-2+49674A>G		intron	N/A	NP_001427749.1
	LIPA	NM_001440821.1		c.-99+49724A>G		intron	N/A	NP_001427750.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IFIT6P	ENST00000418257.1	TSL:6	n.774T>C		non_coding_transcript_exon	Exon 1 of 1
	LIPA	ENST00000371837.5	TSL:2	c.61+49724A>G		intron	N/A	ENSP00000360903.1
	IFIT3	ENST00000679438.1		c.-15-6372T>C		intron	N/A	ENSP00000506015.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.0000134 AC: 1 AN: 74442 Hom.: 0 Cov.: 0 AF XY: 0.0000232 AC XY: 1 AN XY: 43036

African (AFR) AF: 0.00 AC: 0 AN: 2116

American (AMR) AF: 0.000118 AC: 1 AN: 8482

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 1218

East Asian (EAS) AF: 0.00 AC: 0 AN: 4736

South Asian (SAS) AF: 0.00 AC: 0 AN: 6974

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9440

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 906

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 37452

Other (OTH) AF: 0.00 AC: 0 AN: 3118

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 1144

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.4
DANN	Benign	0.87
PhyloP100		1.7

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;