9-21304804-G-A

Variant names:

• chr9-21304804-G-A
• rs10757212
• NM_002169.3:c.453C>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_002169.3(IFNA5):​c.453C>T​(p.Thr151Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.227 in 1,613,846 control chromosomes in the GnomAD database, including 44,825 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 0.27 (5924 hom., cov: 32)
  • Exomes 𝑓: 0.22 (38901 hom.)
• Consequence: IFNA5 NM_002169.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.10
• Publications: 25 publications found

Genes affected

IFNA5 (HGNC:5426): (interferon alpha 5) Predicted to enable cytokine activity and type I interferon receptor binding activity. Predicted to be involved in several processes, including B cell activation; lymphocyte activation involved in immune response; and positive regulation of peptidyl-serine phosphorylation of STAT protein. Predicted to be located in extracellular region. Predicted to be active in extracellular space. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000301340 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP7: Synonymous conserved (PhyloP=-1.1 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.456 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002169.3. 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
	IFNA5	NM_002169.3	MANE Select	c.453C>T	p.Thr151Thr	synonymous	Exon 1 of 1	NP_002160.1	P01569

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IFNA5	ENST00000610521.2	TSL:6 MANE Select	c.453C>T	p.Thr151Thr	synonymous	Exon 1 of 1	ENSP00000484479.1	P01569
	ENSG00000301340	ENST00000778316.1		n.385-31817G>A		intron	N/A
	ENSG00000301340	ENST00000778317.1		n.539-31817G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.268 AC: 40775 AN: 151936 Hom.: 5916 Cov.: 32

Gnomad AFR AF: 0.349

Gnomad AMI AF: 0.168

Gnomad AMR AF: 0.310

Gnomad ASJ AF: 0.239

Gnomad EAS AF: 0.472

Gnomad SAS AF: 0.162

Gnomad FIN AF: 0.209

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.214

Gnomad OTH AF: 0.266

GnomAD2 exomes AF: 0.252 AC: 63386 AN: 251412 AF XY: 0.238

Gnomad AFR exome AF: 0.357

Gnomad AMR exome AF: 0.357

Gnomad ASJ exome AF: 0.226

Gnomad EAS exome AF: 0.480

Gnomad FIN exome AF: 0.207

Gnomad NFE exome AF: 0.205

Gnomad OTH exome AF: 0.244

GnomAD4 exome AF: 0.222 AC: 324768 AN: 1461792 Hom.: 38901 Cov.: 33 AF XY: 0.219 AC XY: 159251 AN XY: 727206

African (AFR) AF: 0.353 AC: 11830 AN: 33474

American (AMR) AF: 0.351 AC: 15701 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.231 AC: 6025 AN: 26136

East Asian (EAS) AF: 0.487 AC: 19314 AN: 39696

South Asian (SAS) AF: 0.158 AC: 13655 AN: 86248

European-Finnish (FIN) AF: 0.204 AC: 10886 AN: 53420

Middle Eastern (MID) AF: 0.221 AC: 1272 AN: 5768

European-Non Finnish (NFE) AF: 0.209 AC: 231914 AN: 1111932

Other (OTH) AF: 0.235 AC: 14171 AN: 60396

GnomAD4 genome AF: 0.269 AC: 40828 AN: 152054 Hom.: 5924 Cov.: 32 AF XY: 0.268 AC XY: 19894 AN XY: 74318

African (AFR) AF: 0.350 AC: 14486 AN: 41432

American (AMR) AF: 0.310 AC: 4745 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.239 AC: 830 AN: 3470

East Asian (EAS) AF: 0.472 AC: 2440 AN: 5174

South Asian (SAS) AF: 0.164 AC: 789 AN: 4818

European-Finnish (FIN) AF: 0.209 AC: 2213 AN: 10572

Middle Eastern (MID) AF: 0.238 AC: 70 AN: 294

European-Non Finnish (NFE) AF: 0.214 AC: 14543 AN: 67978

Other (OTH) AF: 0.265 AC: 559 AN: 2112

Alfa AF: 0.237 Hom.: 1924

Bravo AF: 0.284

Asia WGS AF: 0.315 AC: 1093 AN: 3478

EpiCase AF: 0.215

EpiControl AF: 0.205

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.5
DANN	Benign	0.34
PhyloP100		-1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs10757212; hg19: chr9-21304803; COSMIC: COSV52386674;