chr5-150847809-T-TTTTG

Variant names:

• chr5-150847809-T-TTTTG
• rs60800371
• NM_001145805.2:c.-307_-304dupGTTT

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001145805.2(IRGM):​c.-307_-304dupGTTT variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000289 in 276,740 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000046 (0 hom., cov: 26)
  • Exomes 𝑓: 0.0000080 (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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001145805.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IRGM	NM_001145805.2	MANE Select	c.-307_-304dupGTTT		5_prime_UTR	Exon 2 of 2	NP_001139277.1	A1A4Y4-1
	IRGM	NM_001346557.2		c.-307_-304dupGTTT		5_prime_UTR	Exon 2 of 4	NP_001333486.1	A1A4Y4-2
	IRGM	NR_170598.1		n.809_812dupGTTT		non_coding_transcript_exon	Exon 2 of 5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IRGM	ENST00000522154.2	TSL:1 MANE Select	c.-307_-304dupGTTT		5_prime_UTR	Exon 2 of 2	ENSP00000428220.1	A1A4Y4-1
	IRGM	ENST00000951736.1		c.-276-31_-276-28dupGTTT		intron	N/A	ENSP00000621795.1

Frequencies

GnomAD3 genomes AF: 0.0000462 AC: 7 AN: 151528 Hom.: 0 Cov.: 26

Gnomad AFR AF: 0.000170

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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 AF: 0.00000799 AC: 1 AN: 125212 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 65620

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

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: 0.00 AC: 0 AN: 6558

South Asian (SAS) AF: 0.00 AC: 0 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

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.0000462 AC: 7 AN: 151528 Hom.: 0 Cov.: 26 AF XY: 0.0000676 AC XY: 5 AN XY: 73924

African (AFR) AF: 0.000170 AC: 7 AN: 41134

American (AMR) AF: 0.00 AC: 0 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

Alfa AF: 0.00 Hom.: 21

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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;