9-21207038-A-T

Variant names:

• chr9-21207038-A-T
• rs10119910
• NM_002171.2:c.60T>A

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_002171.2(IFNA10):​c.60T>A​(p.Cys20*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.213 in 1,508,488 control chromosomes in the GnomAD database, including 47,160 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 0.28 (6515 hom., cov: 31)
  • Exomes 𝑓: 0.21 (40645 hom.)
• Consequence: IFNA10 NM_002171.2 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.638
• Publications: 28 publications found

Genes affected

IFNA10 (HGNC:5418): (interferon alpha 10) This gene encodes a protein that belongs to the type I interferon family of proteins, and is located in a cluster of alpha interferon genes on chromosome 9. Interferons are small regulatory molecules that function in cell signaling in response to viruses and other pathogens or tumor cells. This gene is intronless and the encoded protein is secreted. [provided by RefSeq, Aug 2013]

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.491 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IFNA10	NM_002171.2	c.60T>A	p.Cys20*	stop_gained	Exon 1 of 1	ENST00000357374.2	NP_002162.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IFNA10	ENST00000357374.2	c.60T>A	p.Cys20*	stop_gained	Exon 1 of 1	6	NM_002171.2	ENSP00000369566.1

Frequencies

GnomAD3 genomes AF: 0.279 AC: 42027 AN: 150904 Hom.: 6506 Cov.: 31

Gnomad AFR AF: 0.376

Gnomad AMI AF: 0.169

Gnomad AMR AF: 0.309

Gnomad ASJ AF: 0.241

Gnomad EAS AF: 0.508

Gnomad SAS AF: 0.199

Gnomad FIN AF: 0.213

Gnomad MID AF: 0.239

Gnomad NFE AF: 0.216

Gnomad OTH AF: 0.269

GnomAD2 exomes AF: 0.216 AC: 49259 AN: 227702 AF XY: 0.203

Gnomad AFR exome AF: 0.330

Gnomad AMR exome AF: 0.304

Gnomad ASJ exome AF: 0.160

Gnomad EAS exome AF: 0.507

Gnomad FIN exome AF: 0.183

Gnomad NFE exome AF: 0.157

Gnomad OTH exome AF: 0.194

GnomAD4 exome AF: 0.206 AC: 279840 AN: 1357462 Hom.: 40645 Cov.: 33 AF XY: 0.204 AC XY: 138193 AN XY: 676962

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.356 AC: 10709 AN: 30068

American (AMR) AF: 0.334 AC: 13985 AN: 41854

Ashkenazi Jewish (ASJ) AF: 0.211 AC: 5227 AN: 24720

East Asian (EAS) AF: 0.541 AC: 20971 AN: 38766

South Asian (SAS) AF: 0.176 AC: 14743 AN: 83578

European-Finnish (FIN) AF: 0.205 AC: 10827 AN: 52914

Middle Eastern (MID) AF: 0.195 AC: 1072 AN: 5494

European-Non Finnish (NFE) AF: 0.186 AC: 189879 AN: 1023496

Other (OTH) AF: 0.220 AC: 12427 AN: 56572

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.279 AC: 42081 AN: 151026 Hom.: 6515 Cov.: 31 AF XY: 0.278 AC XY: 20495 AN XY: 73774

African (AFR) AF: 0.376 AC: 15355 AN: 40864

American (AMR) AF: 0.309 AC: 4696 AN: 15186

Ashkenazi Jewish (ASJ) AF: 0.241 AC: 834 AN: 3466

East Asian (EAS) AF: 0.507 AC: 2575 AN: 5074

South Asian (SAS) AF: 0.201 AC: 966 AN: 4814

European-Finnish (FIN) AF: 0.213 AC: 2251 AN: 10552

Middle Eastern (MID) AF: 0.240 AC: 70 AN: 292

European-Non Finnish (NFE) AF: 0.216 AC: 14615 AN: 67760

Other (OTH) AF: 0.268 AC: 565 AN: 2106

Alfa AF: 0.168 Hom.: 715

Bravo AF: 0.296

ExAC AF: 0.225 AC: 27227

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Uncertain	-0.060
CADD	Pathogenic	36
DANN	Uncertain	0.99
Eigen	Benign	-0.33
Eigen_PC	Benign	-0.71
FATHMM_MKL	Benign	0.0023	N
PhyloP100		-0.64
Vest4		0.023
GERP RS		-0.94
PromoterAI		0.012	Neutral
Mutation Taster		=187/13	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs10119910; hg19: chr9-21207037; COSMIC: COSV53330839; COSMIC: COSV53330839;