chr9-21440417-A-G

Position:

• chr9-21440417-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The ENST00000698348.1(MIR31HG):​n.838T>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0393 in 1,520,846 control chromosomes in the GnomAD database, including 1,404 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 0.034 (117 hom., cov: 30)
  • Exomes 𝑓: 0.040 (1287 hom.)
• Consequence: MIR31HG ENST00000698348.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.30

Genes affected

MIR31HG (HGNC:):

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0339 (5166/152306) while in subpopulation NFE AF= 0.0434 (2954/68020). AF 95% confidence interval is 0.0421. There are 117 homozygotes in gnomad4. There are 2511 alleles in male gnomad4 subpopulation. Median coverage is 30. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 117 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
		n.21440417A>G		intergenic_region
IFNA1	NM_024013.3	c.-91A>G		upstream_gene_variant		ENST00000276927.3	NP_076918.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IFNA1	ENST00000276927.3	c.-91A>G		upstream_gene_variant		6	NM_024013.3	ENSP00000276927.1

Frequencies

GnomAD3 genomes AF: 0.0339 AC: 5163 AN: 152188 Hom.: 116 Cov.: 30

Gnomad AFR AF: 0.0186

Gnomad AMI AF: 0.0779

Gnomad AMR AF: 0.0323

Gnomad ASJ AF: 0.0634

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0309

Gnomad FIN AF: 0.0368

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0434

Gnomad OTH AF: 0.0464

GnomAD4 exome AF: 0.0399 AC: 54626 AN: 1368540 Hom.: 1287 Cov.: 25 AF XY: 0.0399 AC XY: 27160 AN XY: 681216

Gnomad4 AFR exome AF: 0.0173

Gnomad4 AMR exome AF: 0.0251

Gnomad4 ASJ exome AF: 0.0674

Gnomad4 EAS exome AF: 0.0000512

Gnomad4 SAS exome AF: 0.0328

Gnomad4 FIN exome AF: 0.0369

Gnomad4 NFE exome AF: 0.0426

Gnomad4 OTH exome AF: 0.0394

GnomAD4 genome AF: 0.0339 AC: 5166 AN: 152306 Hom.: 117 Cov.: 30 AF XY: 0.0337 AC XY: 2511 AN XY: 74470

Gnomad4 AFR AF: 0.0187

Gnomad4 AMR AF: 0.0322

Gnomad4 ASJ AF: 0.0634

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0307

Gnomad4 FIN AF: 0.0368

Gnomad4 NFE AF: 0.0434

Gnomad4 OTH AF: 0.0459

Alfa AF: 0.0289 Hom.: 18

Bravo AF: 0.0324

Asia WGS AF: 0.0140 AC: 47 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.11
DANN	Benign	0.71

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs28383793; hg19: chr9-21440416;