rs1758566

Positions:

• chr9-21440491-T-C

Variant summary

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

The NM_024013.3(IFNA1):​c.-17T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.096 in 1,612,118 control chromosomes in the GnomAD database, including 7,825 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 0.12 (1175 hom., cov: 29)
  • Exomes 𝑓: 0.094 (6650 hom.)
• Consequence: IFNA1 NM_024013.3 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.169

Genes affected

IFNA1 (HGNC:5417): (interferon alpha 1) This gene is a member of the alpha interferon gene cluster on chromosome 9. The encoded cytokine is a member of the type I interferon family that is produced in response to viral infection as a key part of the innate immune response with potent antiviral, antiproliferative and immunomodulatory properties. This cytokine, like other type I interferons, binds a plasma membrane receptor made of IFNAR1 and IFNAR2 that is ubiquitously expressed, and thus is able to act on virtually all body cells. This cytokine is upregulated in preeclamptic placentas and is thought to be a mediator of preeclampsia. [provided by RefSeq, Aug 2020]

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.176 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IFNA1	NM_024013.3	c.-17T>C		5_prime_UTR_variant	1/1	ENST00000276927.3	NP_076918.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IFNA1	ENST00000276927.3	c.-17T>C		5_prime_UTR_variant	1/1		NM_024013.3	ENSP00000276927	P1
MIR31HG	ENST00000698343.1	n.103-19799A>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.119 AC: 18102 AN: 152000 Hom.: 1171 Cov.: 29

Gnomad AFR AF: 0.179

Gnomad AMI AF: 0.0976

Gnomad AMR AF: 0.116

Gnomad ASJ AF: 0.0953

Gnomad EAS AF: 0.121

Gnomad SAS AF: 0.0980

Gnomad FIN AF: 0.103

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.0891

Gnomad OTH AF: 0.109

GnomAD3 exomes AF: 0.100 AC: 25046 AN: 250132 Hom.: 1342 AF XY: 0.0998 AC XY: 13490 AN XY: 135196

Gnomad AFR exome AF: 0.182

Gnomad AMR exome AF: 0.0821

Gnomad ASJ exome AF: 0.113

Gnomad EAS exome AF: 0.118

Gnomad SAS exome AF: 0.101

Gnomad FIN exome AF: 0.101

Gnomad NFE exome AF: 0.0897

Gnomad OTH exome AF: 0.0939

GnomAD4 exome AF: 0.0936 AC: 136633 AN: 1460000 Hom.: 6650 Cov.: 32 AF XY: 0.0936 AC XY: 67993 AN XY: 726336

Gnomad4 AFR exome AF: 0.181

Gnomad4 AMR exome AF: 0.0858

Gnomad4 ASJ exome AF: 0.110

Gnomad4 EAS exome AF: 0.115

Gnomad4 SAS exome AF: 0.0998

Gnomad4 FIN exome AF: 0.0980

Gnomad4 NFE exome AF: 0.0891

Gnomad4 OTH exome AF: 0.101

GnomAD4 genome AF: 0.119 AC: 18126 AN: 152118 Hom.: 1175 Cov.: 29 AF XY: 0.119 AC XY: 8866 AN XY: 74364

Gnomad4 AFR AF: 0.179

Gnomad4 AMR AF: 0.116

Gnomad4 ASJ AF: 0.0953

Gnomad4 EAS AF: 0.121

Gnomad4 SAS AF: 0.0976

Gnomad4 FIN AF: 0.103

Gnomad4 NFE AF: 0.0891

Gnomad4 OTH AF: 0.107

Alfa AF: 0.101 Hom.: 137

Bravo AF: 0.123

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	8.1
DANN	Benign	0.82

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: rs1758566; hg19: chr9-21440490; COSMIC: COSV52806474;