ENST00000621160.5:c.218C>A

Variant names:

• chr14-94115877-C-A
• rs762591542
• NM_001130080.3:c.218C>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The ENST00000621160.5(IFI27):​c.218C>A​(p.Ala73Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,447,942 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A73V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: IFI27 ENST00000621160.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.142
• Publications: 2 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000621160.5. 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.218C>A	p.Ala73Glu	missense	Exon 4 of 5	NP_001123552.1	P40305-2
	IFI27	NM_001288952.2		c.218C>A	p.Ala73Glu	missense	Exon 5 of 6	NP_001275881.1	P40305-2
	IFI27	NM_001288956.2		c.218C>A	p.Ala73Glu	missense	Exon 4 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.218C>A	p.Ala73Glu	missense	Exon 4 of 5	ENSP00000483498.1	P40305-2
	IFI27	ENST00000612813.4	TSL:3	c.218C>A	p.Ala73Glu	missense	Exon 4 of 5	ENSP00000483430.1	P40305-2
	IFI27	ENST00000616764.5	TSL:2	c.218C>A	p.Ala73Glu	missense	Exon 5 of 6	ENSP00000477753.1	P40305-2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000138 AC: 2 AN: 1447942 Hom.: 0 Cov.: 34 AF XY: 0.00000278 AC XY: 2 AN XY: 718818

African (AFR) AF: 0.00 AC: 0 AN: 33176

American (AMR) AF: 0.00 AC: 0 AN: 43026

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25830

East Asian (EAS) AF: 0.00 AC: 0 AN: 39178

South Asian (SAS) AF: 0.0000119 AC: 1 AN: 83960

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52200

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5752

European-Non Finnish (NFE) AF: 9.05e-7 AC: 1 AN: 1104928

Other (OTH) AF: 0.00 AC: 0 AN: 59892

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.40
BayesDel_addAF	Pathogenic	0.24	D
BayesDel_noAF	Uncertain	0.11
CADD	Benign	11
DANN	Benign	0.63
DEOGEN2	Benign	0.20	T
Eigen	Benign	-0.45
Eigen_PC	Benign	-0.76
FATHMM_MKL	Benign	0.098	N
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.031	D
MetaRNN	Uncertain	0.49	T
MetaSVM	Benign	-0.85	T
PhyloP100		-0.14
PrimateAI	Benign	0.28	T
Sift4G	Uncertain	0.016	D
Vest4		0.48
MutPred		0.64		Loss of MoRF binding (P = 0.091)
MVP		0.27
ClinPred		0.48	T
GERP RS		-2.6
Varity_R		0.083
gMVP		0.35
Mutation Taster		=96/4	polymorphism

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: rs762591542; hg19: chr14-94582214;