9-21440917-C-T

Position:

• chr9-21440917-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_024013.3(IFNA1):​c.410C>T​(p.Ala137Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0188 in 144,310 control chromosomes in the GnomAD database, including 41 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.019 (41 hom., cov: 25)
  • Exomes 𝑓: 0.0037 (57 hom.)
  • Failed GnomAD Quality Control
• Consequence: IFNA1 NM_024013.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.436

Genes affected

IFNA1 (HGNC:5417): (interferon alpha 1) This gene is a member of the alpha interferon gene cluster on chromosome 9. The encoded cytokine is a member of the type I interferon family that is produced in response to viral infection as a key part of the innate immune response with potent antiviral, antiproliferative and immunomodulatory properties. This cytokine, like other type I interferons, binds a plasma membrane receptor made of IFNAR1 and IFNAR2 that is ubiquitously expressed, and thus is able to act on virtually all body cells. This cytokine is upregulated in preeclamptic placentas and is thought to be a mediator of preeclampsia. [provided by RefSeq, Aug 2020]

MIR31HG (HGNC:37187): (MIR31 host gene) This gene produces a long non-coding RNA that acts as a host gene for miR-31. This transcript may be involved in cellular pluripotency and regulate the differentiation of myoblasts and other tissues. This RNA was found to interact with Polycomb repressive proteins to repression transcription of genes involves in cell senescence. [provided by RefSeq, Dec 2017]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0036209226).
• BP6: Variant 9-21440917-C-T is Benign according to our data. Variant chr9-21440917-C-T is described in ClinVar as [Benign]. Clinvar id is 790065.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0574 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IFNA1	NM_024013.3	c.410C>T	p.Ala137Val	missense_variant	1/1	ENST00000276927.3	NP_076918.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IFNA1	ENST00000276927.3	c.410C>T	p.Ala137Val	missense_variant	1/1		NM_024013.3	ENSP00000276927	P1
MIR31HG	ENST00000698343.1	n.103-20225G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0187 AC: 2702 AN: 144194 Hom.: 40 Cov.: 25

Gnomad AFR AF: 0.0595

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0124

Gnomad ASJ AF: 0.0112

Gnomad EAS AF: 0.00119

Gnomad SAS AF: 0.00213

Gnomad FIN AF: 0.000104

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.00249

Gnomad OTH AF: 0.0203

GnomAD3 exomes AF: 0.00648 AC: 1556 AN: 240248 Hom.: 27 AF XY: 0.00528 AC XY: 689 AN XY: 130532

Gnomad AFR exome AF: 0.0672

Gnomad AMR exome AF: 0.00436

Gnomad ASJ exome AF: 0.0102

Gnomad EAS exome AF: 0.000829

Gnomad SAS exome AF: 0.000887

Gnomad FIN exome AF: 0.000143

Gnomad NFE exome AF: 0.00237

Gnomad OTH exome AF: 0.00636

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00369 AC: 5357 AN: 1451106 Hom.: 57 Cov.: 31 AF XY: 0.00339 AC XY: 2443 AN XY: 720914

Gnomad4 AFR exome AF: 0.0670

Gnomad4 AMR exome AF: 0.00594

Gnomad4 ASJ exome AF: 0.0114

Gnomad4 EAS exome AF: 0.000809

Gnomad4 SAS exome AF: 0.000891

Gnomad4 FIN exome AF: 0.0000942

Gnomad4 NFE exome AF: 0.00174

Gnomad4 OTH exome AF: 0.00790

GnomAD4 genome AF: 0.0188 AC: 2707 AN: 144310 Hom.: 41 Cov.: 25 AF XY: 0.0181 AC XY: 1264 AN XY: 69874

Gnomad4 AFR AF: 0.0595

Gnomad4 AMR AF: 0.0124

Gnomad4 ASJ AF: 0.0112

Gnomad4 EAS AF: 0.00119

Gnomad4 SAS AF: 0.00213

Gnomad4 FIN AF: 0.000104

Gnomad4 NFE AF: 0.00249

Gnomad4 OTH AF: 0.0201

Alfa AF: 0.00315 Hom.: 2

Bravo AF: 0.0238

ESP6500AA AF: 0.0660 AC: 264

ESP6500EA AF: 0.00304 AC: 25

ExAC AF: 0.00746 AC: 902

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.079
BayesDel_addAF	Benign	-0.75	T
BayesDel_noAF	Benign	-0.84
CADD	Benign	4.8
DANN	Benign	0.86
DEOGEN2	Benign	0.029	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.014	N
LIST_S2	Benign	0.26	T
MetaRNN	Benign	0.0036	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	-0.28	N
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.20	T
PROVEAN	Benign	-0.58	N
REVEL	Benign	0.0050
Sift	Benign	0.13	T
Sift4G	Benign	0.23	T
Polyphen		0.0020	B
Vest4		0.051
MVP		0.043
MPC		1.4
ClinPred		0.0016	T
GERP RS		0.51
Varity_R		0.098
gMVP		0.024

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

Publications

LitVar

Other links and lift over

dbSNP: rs2230050; hg19: chr9-21440916; COSMIC: COSV52806419;