Variant rs145187664 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_StrongBP6_ModerateBP7

The NM_022168.4(IFIH1):c.2784C>T(p.His928=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000193 in 1,606,744 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00059 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00015 ( 1 hom. )

Consequence

IFIH1
NM_022168.4 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.13

Variant links:

Genes affected

IFIH1 (HGNC:18873): (interferon induced with helicase C domain 1) IFIH1 encodes MDA5 which is an intracellular sensor of viral RNA that triggers the innate immune response. Sensing RNA length and secondary structure, MDA5 binds dsRNA oligonucleotides with a modified DExD/H-box helicase core and a C-terminal domain, thus leading to a proinflammatory response that includes interferons. It has been shown that Coronaviruses (CoVs) as well as various other virus families, are capable of evading the MDA5-dependent interferon response, thus impeding the activation of the innate immune response to infection. MDA5 has also been shown to play an important role in enhancing natural killer cell function in malaria infection. In addition to its protective role in antiviral responses, MDA5 has been implicated in autoimmune and autoinflammatory diseases such as type 1 diabetes, systemic lupus erythematosus, and Aicardi-Goutieres syndrome[provided by RefSeq, Jul 2020]

IFIH1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -7 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.47).

BP6

Variant 2-162268110-G-A is Benign according to our data. Variant chr2-162268110-G-A is described in ClinVar as [Benign]. Clinvar id is 474955.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=1.13 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IFIH1	NM_022168.4 linkuse as main transcript	c.2784C>T	p.His928=	synonymous_variant	14/16	ENST00000649979.2	NP_071451.2
IFIH1	XM_047445407.1 linkuse as main transcript	c.2067C>T	p.His689=	synonymous_variant	13/15		XP_047301363.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IFIH1	ENST00000649979.2 linkuse as main transcript	c.2784C>T	p.His928=	synonymous_variant	14/16		NM_022168.4	ENSP00000497271	P1	Q9BYX4-1

Frequencies

GnomAD3 genomes

AF:

0.000591

AC:

AN:

152166

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000796

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000982

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00339

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.000956

GnomAD3 exomes

AF:

0.000310

AC:

AN:

245016

Hom.:

AF XY:

0.000302

AC XY:

AN XY:

132300

show subpopulations

Gnomad AFR exome

AF:

0.000747

Gnomad AMR exome

AF:

0.0000605

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000347

Gnomad FIN exome

AF:

0.00209

Gnomad NFE exome

AF:

0.000134

Gnomad OTH exome

AF:

0.000168

GnomAD4 exome

AF:

0.000151

AC:

220

AN:

1454460

Hom.:

Cov.:

AF XY:

0.000163

AC XY:

118

AN XY:

723202

show subpopulations

Gnomad4 AFR exome

AF:

0.000363

Gnomad4 AMR exome

AF:

0.000138

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000119

Gnomad4 FIN exome

AF:

0.00159

Gnomad4 NFE exome

AF:

0.0000865

Gnomad4 OTH exome

AF:

0.000333

GnomAD4 genome

AF:

0.000591

AC:

AN:

152284

Hom.:

Cov.:

AF XY:

0.000765

AC XY:

AN XY:

74472

show subpopulations

Gnomad4 AFR

AF:

0.000794

Gnomad4 AMR

AF:

0.000981

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00339

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.000946

Alfa

AF:

0.000176

Hom.:

Bravo

AF:

0.000487

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Aicardi-Goutieres syndrome 7;C4225427:Singleton-Merten syndrome 1

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 25, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.47

CADD

Benign

6.2

DANN

Benign

0.50

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

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