5-150847809-TTTTG-TTTTGTTTGTTTGTTTGTTTGTTTGTTTG

Variant names:

• chr5-150847809-T-TTTTGTTTGTTTGTTTGTTTGTTTG
• rs60800371
• NM_001145805.2:c.-304_-303insGTTTGTTTGTTTGTTTGTTTGTTT

Variant summary

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

The NM_001145805.2(IRGM):​c.-304_-303insGTTTGTTTGTTTGTTTGTTTGTTT variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000066 in 151,528 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 0.0000066 (0 hom., cov: 26)
• 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_-303insGTTTGTTTGTTTGTTTGTTTGTTT		5_prime_UTR_variant	Exon 2 of 2	ENST00000522154.2	NP_001139277.1
IRGM	NR_170598.1	n.812_813insGTTTGTTTGTTTGTTTGTTTGTTT		non_coding_transcript_exon_variant	Exon 2 of 5
IRGM	NM_001346557.2	c.-304_-303insGTTTGTTTGTTTGTTTGTTTGTTT		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_-303insGTTTGTTTGTTTGTTTGTTTGTTT		5_prime_UTR_variant	Exon 2 of 2	1	NM_001145805.2	ENSP00000428220.1

Frequencies

GnomAD3 genomes AF: 0.00000660 AC: 1 AN: 151528 Hom.: 0 Cov.: 26

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000657

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 0

GnomAD4 genome AF: 0.00000660 AC: 1 AN: 151528 Hom.: 0 Cov.: 26 AF XY: 0.00 AC XY: 0 AN XY: 73924

African (AFR) AF: 0.00 AC: 0 AN: 41134

American (AMR) AF: 0.0000657 AC: 1 AN: 15226

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5126

South Asian (SAS) AF: 0.00 AC: 0 AN: 4794

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

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67940

Other (OTH) AF: 0.00 AC: 0 AN: 2084

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;