Genetic Variant IFNA10:p.Gln85* (chr9-21206845-G-A) – ACMG Classification: Likely_benign (-3 pts)

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 1P and 4B. PP5BS2

The NM_002171.2(IFNA10):c.253C>T(p.Gln85*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000508 in 1,613,530 control chromosomes in the GnomAD database, including 14 homozygotes. Variant has been reported in ClinVar as Likely risk allele (no stars).

Frequency

Genomes: 𝑓 0.0030 ( 6 hom., cov: 31)

Exomes 𝑓: 0.00024 ( 8 hom. )

Consequence

IFNA10
NM_002171.2 stop_gained

Scores

Clinical Significance

Likely risk allele no assertion criteria provided P:1

Conservation

PhyloP100: 0.566

Variant links:

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]

IFNA10 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -3 ACMG points.

PP5

Variant 9-21206845-G-A is Pathogenic according to our data. Variant chr9-21206845-G-A is described in ClinVar as [Likely_risk_allele]. Clinvar id is 2428777.Status of the report is no_assertion_criteria_provided, 0 stars. We mark this variant Likely_pathogenic, oryginal submission is: [Likely_risk_allele].

BS2

High Homozygotes in GnomAd4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IFNA10	NM_002171.2 link	c.253C>T	p.Gln85*	stop_gained	Exon 1 of 1	ENST00000357374.2	NP_002162.1	P01566A0A7R8C2Z1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IFNA10	ENST00000357374.2 link	c.253C>T	p.Gln85*	stop_gained	Exon 1 of 1	6	NM_002171.2	ENSP00000369566.1		P01566

Frequencies

GnomAD3 genomes

AF:

0.00306

AC:

465

AN:

151754

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0108

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000985

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00239

GnomAD2 exomes

AF:

0.000729

AC:

182

AN:

249636

AF XY:

0.000481

show subpopulations

Gnomad AFR exome

AF:

0.0100

Gnomad AMR exome

AF:

0.000612

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000330

GnomAD4 exome

AF:

0.000244

AC:

357

AN:

1461658

Hom.:

Cov.:

AF XY:

0.000172

AC XY:

125

AN XY:

727136

show subpopulations

Gnomad4 AFR exome

AF:

0.00887

AC:

297

AN:

33466

Gnomad4 AMR exome

AF:

0.000514

AC:

AN:

44710

Gnomad4 ASJ exome

AF:

0.00

AC:

AN:

26130

Gnomad4 EAS exome

AF:

0.00

AC:

AN:

39698

Gnomad4 SAS exome

AF:

0.0000116

AC:

AN:

86250

Gnomad4 FIN exome

AF:

0.00

AC:

AN:

53418

Gnomad4 NFE exome

AF:

0.00000180

AC:

AN:

1111852

Gnomad4 Remaining exome

AF:

0.000480

AC:

AN:

60372

Heterozygous variant carriers

106

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00305

AC:

463

AN:

151872

Hom.:

Cov.:

AF XY:

0.00284

AC XY:

211

AN XY:

74224

show subpopulations

Gnomad4 AFR

AF:

0.0107

AC:

0.0106754

AN:

0.0106754

Gnomad4 AMR

AF:

0.000984

AC:

0.000983994

AN:

0.000983994

Gnomad4 ASJ

AF:

0.00

AC:

AN:

Gnomad4 EAS

AF:

0.00

AC:

AN:

Gnomad4 SAS

AF:

0.00

AC:

AN:

Gnomad4 FIN

AF:

0.00

AC:

AN:

Gnomad4 NFE

AF:

0.0000294

AC:

0.0000294196

AN:

0.0000294196

Gnomad4 OTH

AF:

0.00237

AC:

0.00236518

AN:

0.00236518

Heterozygous variant carriers

100

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00167

Hom.:

Bravo

AF:

0.00311

ESP6500AA

AF:

0.00841

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000898

AC:

109

ClinVar

Significance: Likely risk allele

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Susceptibility to severe COVID-19

Pathogenic:1

Jul 01, 2022

Al Jalila Children’s Genomics Center, Al Jalila Childrens Speciality Hospital

Significance:Likely risk allele

Review Status:no assertion criteria provided

Collection Method:research

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Uncertain

0.14

BayesDel_noAF

Pathogenic

0.44

CADD

Pathogenic

DANN

Uncertain

1.0

Eigen

Uncertain

0.28

Eigen_PC

Benign

-0.065

FATHMM_MKL

Benign

0.090

Vest4

0.019

GERP RS

1.7

Mutation Taster

=182/18

polymorphism

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over