rs2039381

Variant names:

• chr9-21481484-G-A
• rs2039381
• NM_176891.5:c.211C>T

Your query was ambiguous. Multiple possible variants found:

• chr9-21481484-G-A
• chr9-21481484-G-C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 27 publications found

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:37187): (MIR31 host gene) This gene produces a long non-coding RNA that acts as a host gene for miR-31. This transcript may be involved in cellular pluripotency and regulate the differentiation of myoblasts and other tissues. This RNA was found to interact with Polycomb repressive proteins to repression transcription of genes involves in cell senescence. [provided by RefSeq, Dec 2017]

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_176891.5. 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
	IFNE	NM_176891.5	MANE Select	c.211C>T	p.Gln71*	stop_gained	Exon 1 of 1	NP_795372.1
	MIR31HG	NR_027054.2		n.311-4192C>T		intron	N/A
	MIR31HG	NR_152877.1		n.52-4192C>T		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IFNE	ENST00000448696.4	TSL:6 MANE Select	c.211C>T	p.Gln71*	stop_gained	Exon 1 of 1	ENSP00000418018.2
	MIR31HG	ENST00000304425.4	TSL:2	n.344-4192C>T		intron	N/A
	MIR31HG	ENST00000654736.2		n.134-4192C>T		intron	N/A

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

GnomAD2 exomes AF: 0.0454 AC: 11338 AN: 249716 AF XY: 0.0472

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 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

African (AFR) AF: 0.0731 AC: 2448 AN: 33478

American (AMR) AF: 0.0516 AC: 2307 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.000765 AC: 20 AN: 26136

East Asian (EAS) AF: 0.182 AC: 7218 AN: 39688

South Asian (SAS) AF: 0.136 AC: 11770 AN: 86250

European-Finnish (FIN) AF: 0.0163 AC: 868 AN: 53402

Middle Eastern (MID) AF: 0.00954 AC: 55 AN: 5768

European-Non Finnish (NFE) AF: 0.00260 AC: 2891 AN: 1111910

Other (OTH) AF: 0.0278 AC: 1681 AN: 60390

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

African (AFR) AF: 0.0666 AC: 2768 AN: 41546

American (AMR) AF: 0.0612 AC: 937 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00115 AC: 4 AN: 3472

East Asian (EAS) AF: 0.182 AC: 944 AN: 5182

South Asian (SAS) AF: 0.155 AC: 745 AN: 4820

European-Finnish (FIN) AF: 0.0185 AC: 196 AN: 10618

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.00347 AC: 236 AN: 68016

Other (OTH) AF: 0.0313 AC: 66 AN: 2112

Alfa AF: 0.0160 Hom.: 399

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 v4.9

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
PhyloP100		0.20
Vest4		0.075
GERP RS		3.8
Mutation Taster		=155/45	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: rs2039381; hg19: chr9-21481483; COSMIC: COSV58641486;