9-21440417-A-G

Variant names:

• chr9-21440417-A-G
• rs28383793
• ENST00000698348.1:n.838T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 publications found

Genes affected

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]

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

Our verdict: Benign. The variant received -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 the male GnomAd4 subpopulation. Median coverage is 30. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 117 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000698348.1. 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
	IFNA1	NM_024013.3	MANE Select	c.-91A>G		upstream_gene	N/A	NP_076918.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MIR31HG	ENST00000698348.1		n.838T>C		non_coding_transcript_exon	Exon 3 of 3
	MIR31HG	ENST00000698343.1		n.103-19725T>C		intron	N/A
	MIR31HG	ENST00000698344.1		n.497-19725T>C		intron	N/A

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

African (AFR) AF: 0.0173 AC: 521 AN: 30154

American (AMR) AF: 0.0251 AC: 844 AN: 33682

Ashkenazi Jewish (ASJ) AF: 0.0674 AC: 1522 AN: 22582

East Asian (EAS) AF: 0.0000512 AC: 2 AN: 39030

South Asian (SAS) AF: 0.0328 AC: 2550 AN: 77642

European-Finnish (FIN) AF: 0.0369 AC: 1919 AN: 52004

Middle Eastern (MID) AF: 0.0455 AC: 247 AN: 5434

European-Non Finnish (NFE) AF: 0.0426 AC: 44792 AN: 1051370

Other (OTH) AF: 0.0394 AC: 2229 AN: 56642

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

African (AFR) AF: 0.0187 AC: 778 AN: 41572

American (AMR) AF: 0.0322 AC: 493 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0634 AC: 220 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.0307 AC: 148 AN: 4822

European-Finnish (FIN) AF: 0.0368 AC: 390 AN: 10608

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

European-Non Finnish (NFE) AF: 0.0434 AC: 2954 AN: 68020

Other (OTH) AF: 0.0459 AC: 97 AN: 2112

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.11
DANN	Benign	0.71
PhyloP100		-2.3
PromoterAI		0.013	Neutral
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs28383793; hg19: chr9-21440416;