5-150847809-TTTTG-TTTTGTTTGTTTG

Position:

• chr5-150847809-TTTTG-TTTTGTTTGTTTG

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The ENST00000522154.2(IRGM):​c.-311_-304dup variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0287 in 276,690 control chromosomes in the GnomAD database, including 599 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.047 (553 hom., cov: 26)
  • Exomes 𝑓: 0.0065 (46 hom.)
• Consequence: IRGM ENST00000522154.2 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.876

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]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.161 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IRGM	NM_001145805.2	c.-311_-304dup		5_prime_UTR_variant	2/2	ENST00000522154.2	NP_001139277.1
IRGM	NM_001346557.2	c.-311_-304dup		5_prime_UTR_variant	2/4		NP_001333486.1
IRGM	NR_170598.1	n.805_812dup		non_coding_transcript_exon_variant	2/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IRGM	ENST00000522154.2	c.-311_-304dup		5_prime_UTR_variant	2/2	1	NM_001145805.2	ENSP00000428220	P1

Frequencies

GnomAD3 genomes AF: 0.0468 AC: 7090 AN: 151486 Hom.: 542 Cov.: 26

Gnomad AFR AF: 0.163

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0139

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00234

Gnomad SAS AF: 0.00563

Gnomad FIN AF: 0.0000949

Gnomad MID AF: 0.00318

Gnomad NFE AF: 0.000721

Gnomad OTH AF: 0.0369

GnomAD4 exome AF: 0.00650 AC: 813 AN: 125086 Hom.: 46 Cov.: 0 AF XY: 0.00593 AC XY: 389 AN XY: 65554

Gnomad4 AFR exome AF: 0.149

Gnomad4 AMR exome AF: 0.0104

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00215

Gnomad4 SAS exome AF: 0.00251

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000536

Gnomad4 OTH exome AF: 0.0100

GnomAD4 genome AF: 0.0471 AC: 7137 AN: 151604 Hom.: 553 Cov.: 26 AF XY: 0.0456 AC XY: 3376 AN XY: 74038

Gnomad4 AFR AF: 0.164

Gnomad4 AMR AF: 0.0138

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00235

Gnomad4 SAS AF: 0.00585

Gnomad4 FIN AF: 0.0000949

Gnomad4 NFE AF: 0.000721

Gnomad4 OTH AF: 0.0375

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs60800371; hg19: chr5-150227371;