rs2988573

Variant names:

• chr9-21350621-G-A
• rs2988573
• NM_021002.2:c.267C>T

Variant summary

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

The NM_021002.2(IFNA6):​c.267C>T​(p.Asn89Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.168 in 1,613,598 control chromosomes in the GnomAD database, including 23,994 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 0.18 (2616 hom., cov: 32)
  • Exomes 𝑓: 0.17 (21378 hom.)
• Consequence: IFNA6 NM_021002.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.111

Genes affected

IFNA6 (HGNC:5427): (interferon alpha 6) 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. Biomarker of anogenital venereal wart. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).
• BP7: Synonymous conserved (PhyloP=-0.111 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.289 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IFNA6	NM_021002.2	c.267C>T	p.Asn89Asn	synonymous_variant	Exon 1 of 1	ENST00000380210.2	NP_066282.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IFNA6	ENST00000380210.2	c.267C>T	p.Asn89Asn	synonymous_variant	Exon 1 of 1	6	NM_021002.2	ENSP00000369558.1
IFNA6	ENST00000259555.5	c.270C>T	p.Asn90Asn	synonymous_variant	Exon 1 of 1	6		ENSP00000259555.5

Frequencies

GnomAD3 genomes AF: 0.181 AC: 27481 AN: 151928 Hom.: 2614 Cov.: 32

Gnomad AFR AF: 0.172

Gnomad AMI AF: 0.151

Gnomad AMR AF: 0.239

Gnomad ASJ AF: 0.202

Gnomad EAS AF: 0.301

Gnomad SAS AF: 0.108

Gnomad FIN AF: 0.191

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.167

Gnomad OTH AF: 0.182

GnomAD3 exomes AF: 0.185 AC: 46387 AN: 251324 Hom.: 4888 AF XY: 0.175 AC XY: 23764 AN XY: 135820

Gnomad AFR exome AF: 0.178

Gnomad AMR exome AF: 0.278

Gnomad ASJ exome AF: 0.189

Gnomad EAS exome AF: 0.304

Gnomad SAS exome AF: 0.108

Gnomad FIN exome AF: 0.186

Gnomad NFE exome AF: 0.158

Gnomad OTH exome AF: 0.170

GnomAD4 exome AF: 0.166 AC: 243308 AN: 1461552 Hom.: 21378 Cov.: 36 AF XY: 0.164 AC XY: 119183 AN XY: 727086

Gnomad4 AFR exome AF: 0.175

Gnomad4 AMR exome AF: 0.271

Gnomad4 ASJ exome AF: 0.194

Gnomad4 EAS exome AF: 0.292

Gnomad4 SAS exome AF: 0.109

Gnomad4 FIN exome AF: 0.182

Gnomad4 NFE exome AF: 0.161

Gnomad4 OTH exome AF: 0.167

GnomAD4 genome AF: 0.181 AC: 27499 AN: 152046 Hom.: 2616 Cov.: 32 AF XY: 0.182 AC XY: 13553 AN XY: 74312

Gnomad4 AFR AF: 0.172

Gnomad4 AMR AF: 0.240

Gnomad4 ASJ AF: 0.202

Gnomad4 EAS AF: 0.301

Gnomad4 SAS AF: 0.110

Gnomad4 FIN AF: 0.191

Gnomad4 NFE AF: 0.167

Gnomad4 OTH AF: 0.182

Alfa AF: 0.170 Hom.: 1038

Bravo AF: 0.186

Asia WGS AF: 0.186 AC: 646 AN: 3478

EpiCase AF: 0.156

EpiControl AF: 0.148

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	2.3
DANN	Benign	0.58

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs2988573; hg19: chr9-21350620; COSMIC: COSV66506200;