rs12376071

Variant names:

• chr9-21166903-A-G
• rs12376071
• NM_002175.2:c.-291T>C

Variant summary

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

The NM_002175.2(IFNA21):​c.-291T>C variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.243 in 151,982 control chromosomes in the GnomAD database, including 5,590 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 0.24 (5590 hom., cov: 32)
• Consequence: IFNA21 NM_002175.2 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.268

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=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.351 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IFNA21	NM_002175.2	c.-291T>C		upstream_gene_variant		ENST00000380225.1	NP_002166.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IFNA21	ENST00000380225.1	c.-291T>C		upstream_gene_variant		6	NM_002175.2	ENSP00000369574.1

Frequencies

GnomAD3 genomes AF: 0.243 AC: 36969 AN: 151862 Hom.: 5595 Cov.: 32

Gnomad AFR AF: 0.0624

Gnomad AMI AF: 0.392

Gnomad AMR AF: 0.251

Gnomad ASJ AF: 0.312

Gnomad EAS AF: 0.199

Gnomad SAS AF: 0.366

Gnomad FIN AF: 0.342

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.326

Gnomad OTH AF: 0.255

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.243 AC: 36965 AN: 151982 Hom.: 5590 Cov.: 32 AF XY: 0.247 AC XY: 18357 AN XY: 74292

Gnomad4 AFR AF: 0.0622

Gnomad4 AMR AF: 0.250

Gnomad4 ASJ AF: 0.312

Gnomad4 EAS AF: 0.199

Gnomad4 SAS AF: 0.365

Gnomad4 FIN AF: 0.342

Gnomad4 NFE AF: 0.326

Gnomad4 OTH AF: 0.257

Alfa AF: 0.270 Hom.: 786

Bravo AF: 0.227

Asia WGS AF: 0.303 AC: 1049 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.8
DANN	Benign	0.75

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs12376071; hg19: chr9-21166902; COSMIC: COSV66518878;