rs2039381

Positions:

• chr9-21481484-G-A

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_176891.5(IFNE):​c.211C>T​(p.Gln71*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0218 in 1,614,016 control chromosomes in the GnomAD database, including 2,126 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 0.039 (287 hom., cov: 32)
  • Exomes 𝑓: 0.020 (1839 hom.)
• Consequence: IFNE NM_176891.5 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.205

Genes affected

IFNE (HGNC:18163): (interferon epsilon) Predicted to enable cytokine activity and type I interferon receptor binding activity. Predicted to be involved in several processes, including B cell activation; defense response to other organism; and lymphocyte activation involved in immune response. Predicted to be active in extracellular space. [provided by Alliance of Genome Resources, Apr 2022]

MIR31HG (HGNC:):

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.173 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IFNE	NM_176891.5	c.211C>T	p.Gln71*	stop_gained	1/1	ENST00000448696.4	NP_795372.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IFNE	ENST00000448696.4	c.211C>T	p.Gln71*	stop_gained	1/1	6	NM_176891.5	ENSP00000418018.2

Frequencies

GnomAD3 genomes AF: 0.0387 AC: 5894 AN: 152154 Hom.: 287 Cov.: 32

Gnomad AFR AF: 0.0666

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0611

Gnomad ASJ AF: 0.00115

Gnomad EAS AF: 0.182

Gnomad SAS AF: 0.155

Gnomad FIN AF: 0.0185

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.00347

Gnomad OTH AF: 0.0321

GnomAD3 exomes AF: 0.0454 AC: 11338 AN: 249716 Hom.: 738 AF XY: 0.0472 AC XY: 6368 AN XY: 134962

Gnomad AFR exome AF: 0.0651

Gnomad AMR exome AF: 0.0504

Gnomad ASJ exome AF: 0.000597

Gnomad EAS exome AF: 0.184

Gnomad SAS exome AF: 0.139

Gnomad FIN exome AF: 0.0184

Gnomad NFE exome AF: 0.00325

Gnomad OTH exome AF: 0.0257

GnomAD4 exome AF: 0.0200 AC: 29258 AN: 1461742 Hom.: 1839 Cov.: 32 AF XY: 0.0231 AC XY: 16814 AN XY: 727168

Gnomad4 AFR exome AF: 0.0731

Gnomad4 AMR exome AF: 0.0516

Gnomad4 ASJ exome AF: 0.000765

Gnomad4 EAS exome AF: 0.182

Gnomad4 SAS exome AF: 0.136

Gnomad4 FIN exome AF: 0.0163

Gnomad4 NFE exome AF: 0.00260

Gnomad4 OTH exome AF: 0.0278

GnomAD4 genome AF: 0.0388 AC: 5901 AN: 152274 Hom.: 287 Cov.: 32 AF XY: 0.0423 AC XY: 3153 AN XY: 74464

Gnomad4 AFR AF: 0.0666

Gnomad4 AMR AF: 0.0612

Gnomad4 ASJ AF: 0.00115

Gnomad4 EAS AF: 0.182

Gnomad4 SAS AF: 0.155

Gnomad4 FIN AF: 0.0185

Gnomad4 NFE AF: 0.00347

Gnomad4 OTH AF: 0.0313

Alfa AF: 0.0114 Hom.: 192

Bravo AF: 0.0404

TwinsUK AF: 0.00297 AC: 11

ALSPAC AF: 0.00493 AC: 19

ESP6500AA AF: 0.0660 AC: 291

ESP6500EA AF: 0.00279 AC: 24

ExAC AF: 0.0449 AC: 5446

Asia WGS AF: 0.126 AC: 438 AN: 3478

EpiCase AF: 0.00376

EpiControl AF: 0.00243

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Pathogenic	0.17
CADD	Pathogenic	32
DANN	Uncertain	1.0
Eigen	Uncertain	0.34
Eigen_PC	Benign	-0.011
FATHMM_MKL	Benign	0.13	N
Vest4		0.075
GERP RS		3.8

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

Publications

LitVar

Other links and lift over

dbSNP: rs2039381; hg19: chr9-21481483; COSMIC: COSV58641486;