rs1125488

Positions:

• chr9-21481557-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_176891.5(IFNE):​c.138A>C​(p.Gln46His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0689 in 1,613,856 control chromosomes in the GnomAD database, including 4,211 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.061 (313 hom., cov: 33)
  • Exomes 𝑓: 0.070 (3898 hom.)
• Consequence: IFNE NM_176891.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.22

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.001611799).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0845 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IFNE	NM_176891.5	c.138A>C	p.Gln46His	missense_variant	1/1	ENST00000448696.4	NP_795372.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IFNE	ENST00000448696.4	c.138A>C	p.Gln46His	missense_variant	1/1	6	NM_176891.5	ENSP00000418018.2

Frequencies

GnomAD3 genomes AF: 0.0614 AC: 9346 AN: 152184 Hom.: 315 Cov.: 33

Gnomad AFR AF: 0.0408

Gnomad AMI AF: 0.0197

Gnomad AMR AF: 0.0885

Gnomad ASJ AF: 0.0426

Gnomad EAS AF: 0.0229

Gnomad SAS AF: 0.0711

Gnomad FIN AF: 0.0747

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0702

Gnomad OTH AF: 0.0420

GnomAD3 exomes AF: 0.0718 AC: 17957 AN: 250206 Hom.: 816 AF XY: 0.0696 AC XY: 9415 AN XY: 135256

Gnomad AFR exome AF: 0.0392

Gnomad AMR exome AF: 0.133

Gnomad ASJ exome AF: 0.0362

Gnomad EAS exome AF: 0.0196

Gnomad SAS exome AF: 0.0712

Gnomad FIN exome AF: 0.0739

Gnomad NFE exome AF: 0.0696

Gnomad OTH exome AF: 0.0628

GnomAD4 exome AF: 0.0697 AC: 101883 AN: 1461554 Hom.: 3898 Cov.: 32 AF XY: 0.0693 AC XY: 50374 AN XY: 727080

Gnomad4 AFR exome AF: 0.0414

Gnomad4 AMR exome AF: 0.125

Gnomad4 ASJ exome AF: 0.0382

Gnomad4 EAS exome AF: 0.0160

Gnomad4 SAS exome AF: 0.0722

Gnomad4 FIN exome AF: 0.0801

Gnomad4 NFE exome AF: 0.0708

Gnomad4 OTH exome AF: 0.0625

GnomAD4 genome AF: 0.0614 AC: 9348 AN: 152302 Hom.: 313 Cov.: 33 AF XY: 0.0615 AC XY: 4580 AN XY: 74460

Gnomad4 AFR AF: 0.0407

Gnomad4 AMR AF: 0.0884

Gnomad4 ASJ AF: 0.0426

Gnomad4 EAS AF: 0.0230

Gnomad4 SAS AF: 0.0716

Gnomad4 FIN AF: 0.0747

Gnomad4 NFE AF: 0.0702

Gnomad4 OTH AF: 0.0416

Alfa AF: 0.0654 Hom.: 890

Bravo AF: 0.0617

TwinsUK AF: 0.0680 AC: 252

ALSPAC AF: 0.0703 AC: 271

ESP6500AA AF: 0.0381 AC: 168

ESP6500EA AF: 0.0703 AC: 605

ExAC AF: 0.0697 AC: 8463

Asia WGS AF: 0.0490 AC: 171 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.79	T
BayesDel_noAF	Benign	-0.80
CADD	Benign	1.3
DANN	Benign	0.88
DEOGEN2	Benign	0.0033	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.022	N
LIST_S2	Benign	0.47	T
MetaRNN	Benign	0.0016	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	1.6	L
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-0.98	N
REVEL	Benign	0.048
Sift	Benign	0.11	T
Sift4G	Benign	0.11	T
Polyphen		0.071	B
Vest4		0.031
MutPred		0.14		Gain of catalytic residue at L48 (P = 0.0637);
MPC		0.015
ClinPred		0.013	T
GERP RS		-8.9
Varity_R		0.14
gMVP		0.20

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: rs1125488; hg19: chr9-21481556; COSMIC: COSV58642888;