chr5-150847809-T-TTTTGTTTG

Variant names:

• chr5-150847809-T-TTTTGTTTG
• rs60800371
• NM_001145805.2:c.-311_-304dupGTTTGTTT

Variant summary

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

The NM_001145805.2(IRGM):​c.-311_-304dupGTTTGTTT variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0287 in 276,690 control chromosomes in the GnomAD database, including 599 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.047 (553 hom., cov: 26)
  • Exomes 𝑓: 0.0065 (46 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 (AFR) allele frequency at 95% confidence interval = 0.161 is higher than 0.05.

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.-311_-304dupGTTTGTTT		5_prime_UTR	Exon 2 of 2	NP_001139277.1	A1A4Y4-1
	IRGM	NM_001346557.2		c.-311_-304dupGTTTGTTT		5_prime_UTR	Exon 2 of 4	NP_001333486.1	A1A4Y4-2
	IRGM	NR_170598.1		n.805_812dupGTTTGTTT		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.-311_-304dupGTTTGTTT		5_prime_UTR	Exon 2 of 2	ENSP00000428220.1	A1A4Y4-1
	IRGM	ENST00000951736.1		c.-276-35_-276-28dupGTTTGTTT		intron	N/A	ENSP00000621795.1

Frequencies

GnomAD3 genomes AF: 0.0468 AC: 7090 AN: 151486 Hom.: 542 Cov.: 26

Gnomad AFR AF: 0.163

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0139

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00234

Gnomad SAS AF: 0.00563

Gnomad FIN AF: 0.0000949

Gnomad MID AF: 0.00318

Gnomad NFE AF: 0.000721

Gnomad OTH AF: 0.0369

GnomAD4 exome AF: 0.00650 AC: 813 AN: 125086 Hom.: 46 Cov.: 0 AF XY: 0.00593 AC XY: 389 AN XY: 65554

African (AFR) AF: 0.149 AC: 596 AN: 4012

American (AMR) AF: 0.0104 AC: 52 AN: 5012

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3482

East Asian (EAS) AF: 0.00215 AC: 14 AN: 6502

South Asian (SAS) AF: 0.00251 AC: 38 AN: 15128

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5344

Middle Eastern (MID) AF: 0.00622 AC: 3 AN: 482

European-Non Finnish (NFE) AF: 0.000536 AC: 42 AN: 78336

Other (OTH) AF: 0.0100 AC: 68 AN: 6788

GnomAD4 genome AF: 0.0471 AC: 7137 AN: 151604 Hom.: 553 Cov.: 26 AF XY: 0.0456 AC XY: 3376 AN XY: 74038

African (AFR) AF: 0.164 AC: 6756 AN: 41214

American (AMR) AF: 0.0138 AC: 211 AN: 15246

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

East Asian (EAS) AF: 0.00235 AC: 12 AN: 5114

South Asian (SAS) AF: 0.00585 AC: 28 AN: 4790

European-Finnish (FIN) AF: 0.0000949 AC: 1 AN: 10532

Middle Eastern (MID) AF: 0.00342 AC: 1 AN: 292

European-Non Finnish (NFE) AF: 0.000721 AC: 49 AN: 67932

Other (OTH) AF: 0.0375 AC: 79 AN: 2106

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
Mutation Taster		=297/3	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;