5-150847216-A-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001145805.2(IRGM):​c.-420A>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0389 in 152,436 control chromosomes in the GnomAD database, including 193 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.039 ( 193 hom., cov: 32)
Exomes 𝑓: 0.055 ( 0 hom. )

Consequence

IRGM
NM_001145805.2 5_prime_UTR

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.356
Variant links:
Genes affected
IRGM (HGNC:29597): (immunity related GTPase M) This gene encodes a member of the p47 immunity-related GTPase family. The encoded protein may play a role in the innate immune response by regulating autophagy formation in response to intracellular pathogens. Polymorphisms that affect the normal expression of this gene are associated with a susceptibility to Crohn's disease and tuberculosis. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Oct 2016]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.99).
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.171 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
IRGMNM_001145805.2 linkuse as main transcriptc.-420A>C 5_prime_UTR_variant 1/2 ENST00000522154.2
IRGMNM_001346557.2 linkuse as main transcriptc.-420A>C 5_prime_UTR_variant 1/4
IRGMNR_170598.1 linkuse as main transcriptn.696A>C non_coding_transcript_exon_variant 1/5

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
IRGMENST00000522154.2 linkuse as main transcriptc.-420A>C 5_prime_UTR_variant 1/21 NM_001145805.2 P1
IRGMENST00000609660.1 linkuse as main transcriptn.414A>C non_coding_transcript_exon_variant 1/1

Frequencies

GnomAD3 genomes
AF:
0.0389
AC:
5921
AN:
152118
Hom.:
194
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0149
Gnomad AMI
AF:
0.126
Gnomad AMR
AF:
0.0305
Gnomad ASJ
AF:
0.0369
Gnomad EAS
AF:
0.181
Gnomad SAS
AF:
0.0627
Gnomad FIN
AF:
0.0328
Gnomad MID
AF:
0.102
Gnomad NFE
AF:
0.0425
Gnomad OTH
AF:
0.0388
GnomAD4 exome
AF:
0.0550
AC:
11
AN:
200
Hom.:
0
Cov.:
0
AF XY:
0.0431
AC XY:
5
AN XY:
116
show subpopulations
Gnomad4 EAS exome
AF:
0.0429
Gnomad4 FIN exome
AF:
0.0714
Gnomad4 NFE exome
AF:
0.0526
Gnomad4 OTH exome
AF:
0.250
GnomAD4 genome
AF:
0.0389
AC:
5917
AN:
152236
Hom.:
193
Cov.:
32
AF XY:
0.0404
AC XY:
3008
AN XY:
74440
show subpopulations
Gnomad4 AFR
AF:
0.0149
Gnomad4 AMR
AF:
0.0305
Gnomad4 ASJ
AF:
0.0369
Gnomad4 EAS
AF:
0.181
Gnomad4 SAS
AF:
0.0627
Gnomad4 FIN
AF:
0.0328
Gnomad4 NFE
AF:
0.0425
Gnomad4 OTH
AF:
0.0379
Alfa
AF:
0.0362
Hom.:
17
Bravo
AF:
0.0395
Asia WGS
AF:
0.0920
AC:
320
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.99
CADD
Benign
2.3
DANN
Benign
0.63

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.

Other links and lift over

dbSNP: rs77724219; hg19: chr5-150226778; API