9-21166005-A-G

Variant names:

• chr9-21166005-A-G
• rs2939
• NM_002175.2:c.*38T>C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002175.2(IFNA21):​c.*38T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.173 in 1,593,902 control chromosomes in the GnomAD database, including 26,464 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 (2691 hom., cov: 32)
  • Exomes 𝑓: 0.17 (23773 hom.)
• Consequence: IFNA21 NM_002175.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.54

Genes affected

IFNA21 (HGNC:5424): (interferon alpha 21) This gene is a member of the alpha interferon gene cluster on the short arm of chromosome 9. Interferons are cytokines produced in response to viral infection that mediate the immune response and interfere with viral replication. The encoded protein is a type I interferon and may play a specific role in the antiviral response to rubella virus. [provided by RefSeq, Sep 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.405 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IFNA21	NM_002175.2	c.*38T>C		3_prime_UTR_variant	Exon 1 of 1	ENST00000380225.1	NP_002166.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IFNA21	ENST00000380225	c.*38T>C		3_prime_UTR_variant	Exon 1 of 1		NM_002175.2	ENSP00000369574.1

Frequencies

GnomAD3 genomes AF: 0.179 AC: 27141 AN: 151960 Hom.: 2690 Cov.: 32

Gnomad AFR AF: 0.145

Gnomad AMI AF: 0.134

Gnomad AMR AF: 0.238

Gnomad ASJ AF: 0.186

Gnomad EAS AF: 0.420

Gnomad SAS AF: 0.109

Gnomad FIN AF: 0.197

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.170

Gnomad OTH AF: 0.183

GnomAD3 exomes AF: 0.195 AC: 46782 AN: 239596 Hom.: 5619 AF XY: 0.185 AC XY: 23993 AN XY: 129504

Gnomad AFR exome AF: 0.147

Gnomad AMR exome AF: 0.287

Gnomad ASJ exome AF: 0.174

Gnomad EAS exome AF: 0.440

Gnomad SAS exome AF: 0.110

Gnomad FIN exome AF: 0.191

Gnomad NFE exome AF: 0.161

Gnomad OTH exome AF: 0.174

GnomAD4 exome AF: 0.173 AC: 248732 AN: 1441824 Hom.: 23773 Cov.: 31 AF XY: 0.170 AC XY: 122043 AN XY: 717024

Gnomad4 AFR exome AF: 0.141

Gnomad4 AMR exome AF: 0.279

Gnomad4 ASJ exome AF: 0.178

Gnomad4 EAS exome AF: 0.437

Gnomad4 SAS exome AF: 0.112

Gnomad4 FIN exome AF: 0.189

Gnomad4 NFE exome AF: 0.164

Gnomad4 OTH exome AF: 0.173

GnomAD4 genome AF: 0.179 AC: 27166 AN: 152078 Hom.: 2691 Cov.: 32 AF XY: 0.180 AC XY: 13405 AN XY: 74356

Gnomad4 AFR AF: 0.145

Gnomad4 AMR AF: 0.239

Gnomad4 ASJ AF: 0.186

Gnomad4 EAS AF: 0.419

Gnomad4 SAS AF: 0.110

Gnomad4 FIN AF: 0.197

Gnomad4 NFE AF: 0.170

Gnomad4 OTH AF: 0.185

Alfa AF: 0.165 Hom.: 2231

Bravo AF: 0.183

Asia WGS AF: 0.235 AC: 818 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.47
DANN	Benign	0.41

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs2939; hg19: chr9-21166004; COSMIC: COSV104430803;