1-27666358-G-T

Variant names:

• chr1-27666358-G-T
• rs1141746
• NM_002038.4:c.*23C>A

Variant summary

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

The NM_002038.4(IFI6):​c.*23C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000859 in 1,163,846 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: 30)
  • Exomes 𝑓: 8.6e-7 (0 hom.)
• Consequence: IFI6 NM_002038.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.821
• Publications: 0 publications found

Genes affected

IFI6 (HGNC:4054): (interferon alpha inducible protein 6) This gene was first identified as one of the many genes induced by interferon. The encoded protein may play a critical role in the regulation of apoptosis. A minisatellite that consists of 26 repeats of a 12 nucleotide repeating element resembling the mammalian splice donor consensus sequence begins near the end of the second exon. Alternatively spliced transcript variants that encode different isoforms by using the two downstream repeat units as splice donor sites have been described. [provided by RefSeq, Jul 2008]

LINC02574 (HGNC:53746): (long intergenic non-protein coding RNA 2574)

ENSG00000294734 (HGNC:):

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).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IFI6	NM_002038.4	c.*23C>A		3_prime_UTR_variant	Exon 5 of 5	ENST00000361157.11	NP_002029.3
IFI6	NM_022873.3	c.*23C>A		3_prime_UTR_variant	Exon 5 of 5		NP_075011.1
IFI6	NM_022872.3	c.*23C>A		3_prime_UTR_variant	Exon 5 of 5		NP_075010.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IFI6	ENST00000361157.11	c.*23C>A		3_prime_UTR_variant	Exon 5 of 5	1	NM_002038.4	ENSP00000354736.6

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 8.59e-7 AC: 1 AN: 1163846 Hom.: 0 Cov.: 21 AF XY: 0.00000170 AC XY: 1 AN XY: 588802

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 27034

American (AMR) AF: 0.00 AC: 0 AN: 40206

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22446

East Asian (EAS) AF: 0.00 AC: 0 AN: 34322

South Asian (SAS) AF: 0.00 AC: 0 AN: 78934

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48314

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4832

European-Non Finnish (NFE) AF: 0.00000116 AC: 1 AN: 858916

Other (OTH) AF: 0.00 AC: 0 AN: 48842

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.4
DANN	Benign	0.55
PhyloP100		0.82

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: rs1141746; hg19: chr1-27992869;