14-94116589-C-G

Variant names:

• chr14-94116589-C-G
• rs2799
• NM_001130080.3:c.*62C>G

Variant summary

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

The NM_001130080.3(IFI27):​c.*62C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0841 in 1,340,828 control chromosomes in the GnomAD database, including 9,035 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 0.10 (1214 hom., cov: 32)
  • Exomes 𝑓: 0.082 (7821 hom.)
• Consequence: IFI27 NM_001130080.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.966
• Publications: 12 publications found

Genes affected

IFI27 (HGNC:5397): (interferon alpha inducible protein 27) Enables RNA polymerase II-specific DNA-binding transcription factor binding activity; identical protein binding activity; and lamin binding activity. Involved in several processes, including cellular protein metabolic process; defense response to other organism; and extrinsic apoptotic signaling pathway. Acts upstream of or within negative regulation of transcription by RNA polymerase II and regulation of protein export from nucleus. Located in mitochondrial membrane and nuclear inner membrane. [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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.392 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001130080.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IFI27	NM_001130080.3	MANE Select	c.*62C>G		3_prime_UTR	Exon 5 of 5	NP_001123552.1	P40305-2
	IFI27	NM_001288952.2		c.*62C>G		3_prime_UTR	Exon 6 of 6	NP_001275881.1	P40305-2
	IFI27	NM_001288956.2		c.*62C>G		3_prime_UTR	Exon 5 of 5	NP_001275885.1	P40305-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IFI27	ENST00000621160.5	TSL:1 MANE Select	c.*62C>G		3_prime_UTR	Exon 5 of 5	ENSP00000483498.1	P40305-2
	IFI27	ENST00000612813.4	TSL:3	c.*62C>G		3_prime_UTR	Exon 5 of 5	ENSP00000483430.1	P40305-2
	IFI27	ENST00000616764.5	TSL:2	c.*62C>G		3_prime_UTR	Exon 6 of 6	ENSP00000477753.1	P40305-2

Frequencies

GnomAD3 genomes AF: 0.103 AC: 15734 AN: 152146 Hom.: 1211 Cov.: 32

Gnomad AFR AF: 0.131

Gnomad AMI AF: 0.0461

Gnomad AMR AF: 0.161

Gnomad ASJ AF: 0.0752

Gnomad EAS AF: 0.407

Gnomad SAS AF: 0.187

Gnomad FIN AF: 0.0748

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.0516

Gnomad OTH AF: 0.103

GnomAD4 exome AF: 0.0817 AC: 97056 AN: 1188564 Hom.: 7821 Cov.: 16 AF XY: 0.0845 AC XY: 50621 AN XY: 598788

African (AFR) AF: 0.132 AC: 3673 AN: 27850

American (AMR) AF: 0.227 AC: 8484 AN: 37306

Ashkenazi Jewish (ASJ) AF: 0.0753 AC: 1797 AN: 23876

East Asian (EAS) AF: 0.429 AC: 15859 AN: 36960

South Asian (SAS) AF: 0.178 AC: 13628 AN: 76706

European-Finnish (FIN) AF: 0.0743 AC: 3733 AN: 50230

Middle Eastern (MID) AF: 0.104 AC: 549 AN: 5298

European-Non Finnish (NFE) AF: 0.0506 AC: 44474 AN: 879188

Other (OTH) AF: 0.0950 AC: 4859 AN: 51150

GnomAD4 genome AF: 0.103 AC: 15747 AN: 152264 Hom.: 1214 Cov.: 32 AF XY: 0.109 AC XY: 8149 AN XY: 74440

African (AFR) AF: 0.131 AC: 5433 AN: 41538

American (AMR) AF: 0.160 AC: 2454 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0752 AC: 261 AN: 3470

East Asian (EAS) AF: 0.406 AC: 2098 AN: 5164

South Asian (SAS) AF: 0.186 AC: 899 AN: 4828

European-Finnish (FIN) AF: 0.0748 AC: 794 AN: 10622

Middle Eastern (MID) AF: 0.0782 AC: 23 AN: 294

European-Non Finnish (NFE) AF: 0.0516 AC: 3509 AN: 68026

Other (OTH) AF: 0.111 AC: 234 AN: 2112

Alfa AF: 0.0221 Hom.: 13

Bravo AF: 0.113

Asia WGS AF: 0.244 AC: 848 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.8
DANN	Benign	0.72
PhyloP100		0.97
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: rs2799; hg19: chr14-94582926; COSMIC: COSV107329988; COSMIC: COSV107329988;