chr1-78628133-A-C

Variant names:

• chr1-78628133-A-C
• rs273259
• NM_006820.4:c.218A>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_006820.4(IFI44L):​c.218A>C​(p.His73Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 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. H73Y) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: IFI44L NM_006820.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.78
• Publications: 0 publications found

Genes affected

IFI44L (HGNC:17817): (interferon induced protein 44 like) Predicted to enable GTP binding activity. Involved in defense response to virus. Predicted to be located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.027380317).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IFI44L	NM_006820.4	c.218A>C	p.His73Pro	missense_variant	Exon 2 of 9	ENST00000370751.10	NP_006811.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IFI44L	ENST00000370751.10	c.218A>C	p.His73Pro	missense_variant	Exon 2 of 9	1	NM_006820.4	ENSP00000359787.4
IFI44L	ENST00000459784.6	c.-296-818A>C		intron_variant	Intron 2 of 8	3		ENSP00000506096.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.094
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	0.0020
DANN	Benign	0.14
DEOGEN2	Benign	0.0010	.;T;.
Eigen	Benign	-2.6
Eigen_PC	Benign	-2.7
FATHMM_MKL	Benign	0.0077	N
LIST_S2	Benign	0.21	T;T;T
M_CAP	Benign	0.0014	T
MetaRNN	Benign	0.027	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	.;N;.
PhyloP100		-4.8
PrimateAI	Benign	0.19	T
PROVEAN	Benign	-1.2	N;N;N
REVEL	Benign	0.034
Sift	Benign	0.24	T;T;T
Sift4G	Benign	0.24	T;T;T
Polyphen		0.0070	.;B;.
Vest4		0.099
MutPred		0.26		Gain of loop (P = 0.0097);Gain of loop (P = 0.0097);.;
MVP		0.048
MPC		0.016
ClinPred		0.098	T
GERP RS		-6.2
PromoterAI		-0.0024	Neutral
Varity_R		0.048
gMVP		0.35
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: rs273259; hg19: chr1-79093818;