5-150847809-TTTTG-TTTTGTTTGTTTGTTTGTTTG

Variant names:

• chr5-150847809-T-TTTTGTTTGTTTGTTTG
• rs60800371
• NM_001145805.2:c.-304_-303insGTTTGTTTGTTTGTTT

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001145805.2(IRGM):​c.-304_-303insGTTTGTTTGTTTGTTT variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000101 in 276,856 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000079 (0 hom., cov: 26)
  • Exomes 𝑓: 0.00013 (0 hom.)
• Consequence: IRGM NM_001145805.2 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.876
• Publications: 3 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IRGM	NM_001145805.2	c.-304_-303insGTTTGTTTGTTTGTTT		5_prime_UTR_variant	Exon 2 of 2	ENST00000522154.2	NP_001139277.1
IRGM	NR_170598.1	n.812_813insGTTTGTTTGTTTGTTT		non_coding_transcript_exon_variant	Exon 2 of 5
IRGM	NM_001346557.2	c.-304_-303insGTTTGTTTGTTTGTTT		5_prime_UTR_variant	Exon 2 of 4		NP_001333486.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IRGM	ENST00000522154.2	c.-304_-303insGTTTGTTTGTTTGTTT		5_prime_UTR_variant	Exon 2 of 2	1	NM_001145805.2	ENSP00000428220.1

Frequencies

GnomAD3 genomes AF: 0.0000792 AC: 12 AN: 151526 Hom.: 0 Cov.: 26

Gnomad AFR AF: 0.0000243

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000975

Gnomad SAS AF: 0.00125

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000128 AC: 16 AN: 125212 Hom.: 0 Cov.: 0 AF XY: 0.000183 AC XY: 12 AN XY: 65620

African (AFR) AF: 0.000249 AC: 1 AN: 4024

American (AMR) AF: 0.00 AC: 0 AN: 5014

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3488

East Asian (EAS) AF: 0.000457 AC: 3 AN: 6558

South Asian (SAS) AF: 0.000792 AC: 12 AN: 15148

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5348

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 484

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 78356

Other (OTH) AF: 0.00 AC: 0 AN: 6792

GnomAD4 genome AF: 0.0000791 AC: 12 AN: 151644 Hom.: 0 Cov.: 26 AF XY: 0.000122 AC XY: 9 AN XY: 74050

African (AFR) AF: 0.0000242 AC: 1 AN: 41256

American (AMR) AF: 0.00 AC: 0 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.000978 AC: 5 AN: 5114

South Asian (SAS) AF: 0.00125 AC: 6 AN: 4788

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10532

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67932

Other (OTH) AF: 0.00 AC: 0 AN: 2106

Alfa AF: 0.00 Hom.: 21

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.88

Splicing

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

Other links and lift over

dbSNP: rs60800371; hg19: chr5-150227371;