5-150846512-A-G

Variant summary

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

The NM_001145805.2(IRGM):​c.-1124A>G variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.206 in 149,886 control chromosomes in the GnomAD database, including 5,553 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 0.21 ( 5553 hom., cov: 32)
Exomes 𝑓: 0.031 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

IRGM
NM_001145805.2 upstream_gene

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.34
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=-0.92).
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.453 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
IRGMNM_001145805.2 linkc.-1124A>G upstream_gene_variant ENST00000522154.2 NP_001139277.1 A1A4Y4-1
IRGMNM_001346557.2 linkc.-1124A>G upstream_gene_variant NP_001333486.1 A1A4Y4-2
IRGMNR_170598.1 linkn.-9A>G upstream_gene_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
IRGMENST00000522154.2 linkc.-1124A>G upstream_gene_variant 1 NM_001145805.2 ENSP00000428220.1 A1A4Y4-1

Frequencies

GnomAD3 genomes
AF:
0.206
AC:
30848
AN:
149768
Hom.:
5532
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.458
Gnomad AMI
AF:
0.0341
Gnomad AMR
AF:
0.148
Gnomad ASJ
AF:
0.158
Gnomad EAS
AF:
0.426
Gnomad SAS
AF:
0.204
Gnomad FIN
AF:
0.0750
Gnomad MID
AF:
0.198
Gnomad NFE
AF:
0.0765
Gnomad OTH
AF:
0.205
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.0313
AC:
1
AN:
32
Hom.:
0
Cov.:
0
AF XY:
0.0417
AC XY:
1
AN XY:
24
show subpopulations
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.206
AC:
30912
AN:
149886
Hom.:
5553
Cov.:
32
AF XY:
0.206
AC XY:
15087
AN XY:
73312
show subpopulations
Gnomad4 AFR
AF:
0.458
Gnomad4 AMR
AF:
0.147
Gnomad4 ASJ
AF:
0.158
Gnomad4 EAS
AF:
0.426
Gnomad4 SAS
AF:
0.204
Gnomad4 FIN
AF:
0.0750
Gnomad4 NFE
AF:
0.0766
Gnomad4 OTH
AF:
0.206
Alfa
AF:
0.135
Hom.:
334
Bravo
AF:
0.231

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.92
CADD
Benign
2.1
DANN
Benign
0.31

Splicing

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: rs11741515; hg19: chr5-150226074; API