NM_176891.5:c.138A>C

Variant names:

• chr9-21481557-T-G
• rs1125488
• NM_176891.5:c.138A>C

Variant summary

Our verdict is Benign. The variant received -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. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• 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
• Publications: 24 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 -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.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IFNE	NM_176891.5	MANE Select	c.138A>C	p.Gln46His	missense	Exon 1 of 1	NP_795372.1
	MIR31HG	NR_027054.2		n.311-4265A>C		intron	N/A
	MIR31HG	NR_152877.1		n.52-4265A>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IFNE	ENST00000448696.4	TSL:6 MANE Select	c.138A>C	p.Gln46His	missense	Exon 1 of 1	ENSP00000418018.2
	MIR31HG	ENST00000304425.4	TSL:2	n.344-4265A>C		intron	N/A
	MIR31HG	ENST00000654736.2		n.134-4265A>C		intron	N/A

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

GnomAD2 exomes AF: 0.0718 AC: 17957 AN: 250206 AF XY: 0.0696

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 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

African (AFR) AF: 0.0414 AC: 1386 AN: 33476

American (AMR) AF: 0.125 AC: 5602 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.0382 AC: 997 AN: 26132

East Asian (EAS) AF: 0.0160 AC: 634 AN: 39694

South Asian (SAS) AF: 0.0722 AC: 6230 AN: 86246

European-Finnish (FIN) AF: 0.0801 AC: 4277 AN: 53368

Middle Eastern (MID) AF: 0.0382 AC: 220 AN: 5766

European-Non Finnish (NFE) AF: 0.0708 AC: 78760 AN: 1111756

Other (OTH) AF: 0.0625 AC: 3777 AN: 60394

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

African (AFR) AF: 0.0407 AC: 1690 AN: 41560

American (AMR) AF: 0.0884 AC: 1353 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0426 AC: 148 AN: 3472

East Asian (EAS) AF: 0.0230 AC: 119 AN: 5182

South Asian (SAS) AF: 0.0716 AC: 346 AN: 4832

European-Finnish (FIN) AF: 0.0747 AC: 793 AN: 10614

Middle Eastern (MID) AF: 0.0510 AC: 15 AN: 294

European-Non Finnish (NFE) AF: 0.0702 AC: 4778 AN: 68018

Other (OTH) AF: 0.0416 AC: 88 AN: 2116

Alfa AF: 0.0651 Hom.: 1564

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 v4.9

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
PhyloP100		-3.2
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
Mutation Taster		=96/4	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: rs1125488; hg19: chr9-21481556; COSMIC: COSV58642888;