9-21367809-C-G

Variant names:

• chr9-21367809-C-G
• rs1460383741
• NM_006900.4:c.202G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006900.4(IFNA13):​c.202G>C​(p.Asp68His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000276 in 1,449,328 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/18 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D68Y) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 24)
  • Exomes 𝑓: 0.0000028 (0 hom.)
• Consequence: IFNA13 NM_006900.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.146
• Publications: 0 publications found

Genes affected

IFNA13 (HGNC:5419): (interferon alpha 13) Predicted to enable cytokine activity and type I interferon receptor binding activity. Predicted to be involved in several processes, including B cell activation; lymphocyte activation involved in immune response; and positive regulation of peptidyl-serine phosphorylation of STAT protein. Predicted to be located in extracellular region. Predicted to be active in extracellular space. [provided by Alliance of Genome Resources, Apr 2022]

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.074224025).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006900.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IFNA13	NM_006900.4	MANE Select	c.202G>C	p.Asp68His	missense	Exon 1 of 1	NP_008831.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IFNA13	ENST00000610660.2	TSL:6 MANE Select	c.202G>C	p.Asp68His	missense	Exon 1 of 1	ENSP00000480467.1	A0A087WWS6
	IFNA13	ENST00000449498.2	TSL:6	c.199G>C	p.Asp67His	missense	Exon 1 of 1	ENSP00000394494.2	P01562
	MIR31HG	ENST00000773559.1		n.584-2721G>C		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD4 exome AF: 0.00000276 AC: 4 AN: 1449328 Hom.: 0 Cov.: 31 AF XY: 0.00000139 AC XY: 1 AN XY: 719760

African (AFR) AF: 0.00 AC: 0 AN: 32486

American (AMR) AF: 0.00 AC: 0 AN: 43470

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25848

East Asian (EAS) AF: 0.00 AC: 0 AN: 39498

South Asian (SAS) AF: 0.00 AC: 0 AN: 85706

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52854

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5600

European-Non Finnish (NFE) AF: 0.00000272 AC: 3 AN: 1104108

Other (OTH) AF: 0.0000167 AC: 1 AN: 59758

GnomAD4 genome Cov.: 24

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	11
DANN	Benign	0.85
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.017	N
LIST_S2	Benign	0.27	T
M_CAP	Benign	0.0035	T
MetaRNN	Benign	0.074	T
MetaSVM	Benign	-1.0	T
PhyloP100		0.15
PrimateAI	Benign	0.33	T
REVEL	Benign	0.013
Sift4G	Benign	0.10	T
Vest4		0.19
MutPred		0.46		Loss of disorder (P = 0.1796)
MVP		0.11
MPC		1.7
ClinPred		0.22	T
GERP RS		-0.48
PromoterAI		-0.012	Neutral
gMVP		0.10
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs1460383741; hg19: chr9-21367808; COSMIC: COSV71924490;