5-150847809-TTTTG-TTTTGTTTGTTTGTTTG

Variant names:

• chr5-150847809-T-TTTTGTTTGTTTG
• rs60800371
• NM_001145805.2:c.-304_-303insGTTTGTTTGTTT

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_001145805.2(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. 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 0.20 (4157 hom., cov: 26)
  • Exomes 𝑓: 0.16 (2459 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: Benign. The variant received -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 rank	MANE	Protein	UniProt
IRGM	NM_001145805.2	c.-304_-303insGTTTGTTTGTTT		5_prime_UTR_variant	Exon 2 of 2	ENST00000522154.2	NP_001139277.1
IRGM	NR_170598.1	n.812_813insGTTTGTTTGTTT		non_coding_transcript_exon_variant	Exon 2 of 5
IRGM	NM_001346557.2	c.-304_-303insGTTTGTTTGTTT		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_-303insGTTTGTTTGTTT		5_prime_UTR_variant	Exon 2 of 2	1	NM_001145805.2	ENSP00000428220.1

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

African (AFR) AF: 0.304 AC: 1218 AN: 4006

American (AMR) AF: 0.153 AC: 768 AN: 5006

Ashkenazi Jewish (ASJ) AF: 0.192 AC: 669 AN: 3484

East Asian (EAS) AF: 0.553 AC: 3614 AN: 6536

South Asian (SAS) AF: 0.209 AC: 3167 AN: 15118

European-Finnish (FIN) AF: 0.0890 AC: 475 AN: 5338

Middle Eastern (MID) AF: 0.254 AC: 123 AN: 484

European-Non Finnish (NFE) AF: 0.106 AC: 8291 AN: 78242

Other (OTH) AF: 0.155 AC: 1049 AN: 6768

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

African (AFR) AF: 0.313 AC: 12905 AN: 41204

American (AMR) AF: 0.171 AC: 2605 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.201 AC: 696 AN: 3468

East Asian (EAS) AF: 0.610 AC: 3116 AN: 5110

South Asian (SAS) AF: 0.265 AC: 1269 AN: 4788

European-Finnish (FIN) AF: 0.114 AC: 1195 AN: 10520

Middle Eastern (MID) AF: 0.298 AC: 87 AN: 292

European-Non Finnish (NFE) AF: 0.123 AC: 8388 AN: 67920

Other (OTH) AF: 0.214 AC: 451 AN: 2104

Alfa AF: 0.0367 Hom.: 21

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.88
Mutation Taster		=300/0	polymorphism (auto)

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; COSMIC: COSV105372879; COSMIC: COSV105372879;