5-150847809-TTTTG-TTTTGTTTGTTTGTTTG

Position:

• chr5-150847809-TTTTG-TTTTGTTTGTTTGTTTG

Variant summary

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

The ENST00000522154.2(IRGM):​c.-304_-303insGTTTGTTTGTTT variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.182 in 276,540 control chromosomes in the GnomAD database, including 6,616 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.20 (4157 hom., cov: 26)
  • Exomes 𝑓: 0.16 (2459 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 (EAS) allele frequency at 95% confidence interval = 0.592 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IRGM	NM_001145805.2	c.-304_-303insGTTTGTTTGTTT		5_prime_UTR_variant	2/2	ENST00000522154.2	NP_001139277.1
IRGM	NM_001346557.2	c.-304_-303insGTTTGTTTGTTT		5_prime_UTR_variant	2/4		NP_001333486.1
IRGM	NR_170598.1	n.812_813insGTTTGTTTGTTT		non_coding_transcript_exon_variant	2/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IRGM	ENST00000522154.2	c.-304_-303insGTTTGTTTGTTT		5_prime_UTR_variant	2/2	1	NM_001145805.2	ENSP00000428220	P1

Frequencies

GnomAD3 genomes AF: 0.204 AC: 30842 AN: 151440 Hom.: 4159 Cov.: 26

Gnomad AFR AF: 0.313

Gnomad AMI AF: 0.159

Gnomad AMR AF: 0.171

Gnomad ASJ AF: 0.201

Gnomad EAS AF: 0.609

Gnomad SAS AF: 0.266

Gnomad FIN AF: 0.114

Gnomad MID AF: 0.299

Gnomad NFE AF: 0.123

Gnomad OTH AF: 0.214

GnomAD4 exome AF: 0.155 AC: 19374 AN: 124982 Hom.: 2459 Cov.: 0 AF XY: 0.162 AC XY: 10618 AN XY: 65494

Gnomad4 AFR exome AF: 0.304

Gnomad4 AMR exome AF: 0.153

Gnomad4 ASJ exome AF: 0.192

Gnomad4 EAS exome AF: 0.553

Gnomad4 SAS exome AF: 0.209

Gnomad4 FIN exome AF: 0.0890

Gnomad4 NFE exome AF: 0.106

Gnomad4 OTH exome AF: 0.155

GnomAD4 genome AF: 0.204 AC: 30856 AN: 151558 Hom.: 4157 Cov.: 26 AF XY: 0.206 AC XY: 15242 AN XY: 74008

Gnomad4 AFR AF: 0.313

Gnomad4 AMR AF: 0.171

Gnomad4 ASJ AF: 0.201

Gnomad4 EAS AF: 0.610

Gnomad4 SAS AF: 0.265

Gnomad4 FIN AF: 0.114

Gnomad4 NFE AF: 0.123

Gnomad4 OTH AF: 0.214

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;