rs10757212

Positions:

• chr9-21304804-G-A
• chr9-21304804-G-C
• chr9-21304804-G-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_002169.3(IFNA5):​c.453C>T​(p.Thr151=) 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

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]

LOC107987053 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IFNA5	NM_002169.3	c.453C>T	p.Thr151=	synonymous_variant	1/1	ENST00000610521.2	NP_002160.1
LOC107987053	XR_001746634.2	n.472-31817G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IFNA5	ENST00000610521.2	c.453C>T	p.Thr151=	synonymous_variant	1/1		NM_002169.3	ENSP00000484479	P1

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

GnomAD3 exomes AF: 0.252 AC: 63386 AN: 251412 Hom.: 9253 AF XY: 0.238 AC XY: 32379 AN XY: 135894

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 SAS exome AF: 0.158

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

Gnomad4 AFR exome AF: 0.353

Gnomad4 AMR exome AF: 0.351

Gnomad4 ASJ exome AF: 0.231

Gnomad4 EAS exome AF: 0.487

Gnomad4 SAS exome AF: 0.158

Gnomad4 FIN exome AF: 0.204

Gnomad4 NFE exome AF: 0.209

Gnomad4 OTH exome AF: 0.235

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

Gnomad4 AFR AF: 0.350

Gnomad4 AMR AF: 0.310

Gnomad4 ASJ AF: 0.239

Gnomad4 EAS AF: 0.472

Gnomad4 SAS AF: 0.164

Gnomad4 FIN AF: 0.209

Gnomad4 NFE AF: 0.214

Gnomad4 OTH AF: 0.265

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.5
DANN	Benign	0.34

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

Publications

LitVar

Other links and lift over

dbSNP: rs10757212; hg19: chr9-21304803; COSMIC: COSV52386674;