rs28383794

Variant names:

• chr9-21440995-C-G
• rs28383794
• NM_024013.3:c.488C>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_024013.3(IFNA1):​c.488C>G​(p.Ala163Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0931 in 1,590,596 control chromosomes in the GnomAD database, including 7,430 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.11 (1178 hom., cov: 28)
  • Exomes 𝑓: 0.091 (6252 hom.)
• Consequence: IFNA1 NM_024013.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.17
• Publications: 9 publications found

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

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.003593564).
• BP6: Variant 9-21440995-C-G is Benign according to our data. Variant chr9-21440995-C-G is described in ClinVar as Benign. ClinVar VariationId is 768285.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.185 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IFNA1	NM_024013.3	c.488C>G	p.Ala163Gly	missense_variant	Exon 1 of 1	ENST00000276927.3	NP_076918.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IFNA1	ENST00000276927.3	c.488C>G	p.Ala163Gly	missense_variant	Exon 1 of 1	6	NM_024013.3	ENSP00000276927.1

Frequencies

GnomAD3 genomes AF: 0.113 AC: 16850 AN: 149738 Hom.: 1174 Cov.: 28

Gnomad AFR AF: 0.188

Gnomad AMI AF: 0.0903

Gnomad AMR AF: 0.0771

Gnomad ASJ AF: 0.105

Gnomad EAS AF: 0.000388

Gnomad SAS AF: 0.0429

Gnomad FIN AF: 0.0629

Gnomad MID AF: 0.140

Gnomad NFE AF: 0.0969

Gnomad OTH AF: 0.117

GnomAD2 exomes AF: 0.0818 AC: 18565 AN: 227076 AF XY: 0.0812

Gnomad AFR exome AF: 0.177

Gnomad AMR exome AF: 0.0578

Gnomad ASJ exome AF: 0.108

Gnomad EAS exome AF: 0.000236

Gnomad FIN exome AF: 0.0677

Gnomad NFE exome AF: 0.0971

Gnomad OTH exome AF: 0.0894

GnomAD4 exome AF: 0.0911 AC: 131210 AN: 1440740 Hom.: 6252 Cov.: 31 AF XY: 0.0900 AC XY: 64531 AN XY: 717094

African (AFR) AF: 0.187 AC: 5830 AN: 31252

American (AMR) AF: 0.0614 AC: 2287 AN: 37244

Ashkenazi Jewish (ASJ) AF: 0.109 AC: 2735 AN: 25180

East Asian (EAS) AF: 0.000277 AC: 11 AN: 39652

South Asian (SAS) AF: 0.0466 AC: 3868 AN: 82936

European-Finnish (FIN) AF: 0.0650 AC: 3458 AN: 53212

Middle Eastern (MID) AF: 0.134 AC: 759 AN: 5684

European-Non Finnish (NFE) AF: 0.0967 AC: 106903 AN: 1106046

Other (OTH) AF: 0.0900 AC: 5359 AN: 59534

GnomAD4 genome AF: 0.113 AC: 16871 AN: 149856 Hom.: 1178 Cov.: 28 AF XY: 0.108 AC XY: 7896 AN XY: 73112

African (AFR) AF: 0.188 AC: 7568 AN: 40216

American (AMR) AF: 0.0770 AC: 1161 AN: 15070

Ashkenazi Jewish (ASJ) AF: 0.105 AC: 362 AN: 3444

East Asian (EAS) AF: 0.000389 AC: 2 AN: 5138

South Asian (SAS) AF: 0.0432 AC: 203 AN: 4702

European-Finnish (FIN) AF: 0.0629 AC: 648 AN: 10310

Middle Eastern (MID) AF: 0.144 AC: 42 AN: 292

European-Non Finnish (NFE) AF: 0.0969 AC: 6563 AN: 67710

Other (OTH) AF: 0.116 AC: 240 AN: 2066

Alfa AF: 0.106 Hom.: 166

Bravo AF: 0.119

ESP6500AA AF: 0.108 AC: 474

ESP6500EA AF: 0.0713 AC: 610

ExAC AF: 0.0833 AC: 10111

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.33
BayesDel_addAF	Benign	-0.56	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.21	T
Eigen	Uncertain	0.62
Eigen_PC	Uncertain	0.48
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Pathogenic	0.97	D
MetaRNN	Benign	0.0036	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Pathogenic	3.9	H
PhyloP100		2.2
PrimateAI	Benign	0.36	T
PROVEAN	Uncertain	-3.8	D
REVEL	Benign	0.20
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.013	D
Polyphen		0.93	P
Vest4		0.25
MPC		2.0
ClinPred		0.043	T
GERP RS		3.2
Varity_R		0.89
gMVP		0.16
Mutation Taster		=89/11	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: rs28383794; hg19: chr9-21440994;