rs764816473

Variant names:

• chr9-21440938-A-G
• rs764816473
• NM_024013.3:c.431A>G

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_024013.3(IFNA1):​c.431A>G​(p.Lys144Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000623 in 1,604,652 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000034 (0 hom., cov: 26)
  • Exomes 𝑓: 0.000065 (0 hom.)
• Consequence: IFNA1 NM_024013.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.184
• Publications: 1 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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.031827837).
• BP6: Variant 9-21440938-A-G is Benign according to our data. Variant chr9-21440938-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 2507580.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024013.3. 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
	IFNA1	NM_024013.3	MANE Select	c.431A>G	p.Lys144Arg	missense	Exon 1 of 1	NP_076918.1	P01562

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IFNA1	ENST00000276927.3	TSL:6 MANE Select	c.431A>G	p.Lys144Arg	missense	Exon 1 of 1	ENSP00000276927.1	P01562
	MIR31HG	ENST00000698348.1		n.317T>C		non_coding_transcript_exon	Exon 3 of 3
	MIR31HG	ENST00000698343.1		n.103-20246T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0000341 AC: 5 AN: 146752 Hom.: 0 Cov.: 26

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000451

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000447

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000488 AC: 12 AN: 246104 AF XY: 0.0000823

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000538

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000652 AC: 95 AN: 1457784 Hom.: 0 Cov.: 31 AF XY: 0.0000717 AC XY: 52 AN XY: 724778

African (AFR) AF: 0.00 AC: 0 AN: 33122

American (AMR) AF: 0.00 AC: 0 AN: 44288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26004

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39636

South Asian (SAS) AF: 0.000209 AC: 18 AN: 86062

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53326

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5692

European-Non Finnish (NFE) AF: 0.0000676 AC: 75 AN: 1109470

Other (OTH) AF: 0.0000166 AC: 1 AN: 60184

GnomAD4 genome AF: 0.0000340 AC: 5 AN: 146868 Hom.: 0 Cov.: 26 AF XY: 0.0000560 AC XY: 4 AN XY: 71412

African (AFR) AF: 0.00 AC: 0 AN: 39300

American (AMR) AF: 0.00 AC: 0 AN: 14504

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3422

East Asian (EAS) AF: 0.00 AC: 0 AN: 5082

South Asian (SAS) AF: 0.000452 AC: 2 AN: 4426

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9906

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000447 AC: 3 AN: 67068

Other (OTH) AF: 0.00 AC: 0 AN: 1964

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000189

ExAC AF: 0.0000248 AC: 3

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.070
BayesDel_addAF	Benign	-0.58	T
BayesDel_noAF	Benign	-0.79
CADD	Benign	5.0
DANN	Benign	0.16
DEOGEN2	Benign	0.040	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.026	N
LIST_S2	Benign	0.48	T
M_CAP	Benign	0.0028	T
MetaRNN	Benign	0.032	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	-0.60	N
PhyloP100		-0.18
PrimateAI	Benign	0.39	T
PROVEAN	Benign	1.5	N
REVEL	Benign	0.13
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.090
MVP		0.043
MPC		1.1
ClinPred		0.022	T
GERP RS		-4.1
PromoterAI		0.046	Neutral
Varity_R		0.060
gMVP		0.045
Mutation Taster		=88/12	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.17		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: rs764816473; hg19: chr9-21440937;