rs34156253

Positions:

• chr5-150846668-A-G
• chr5-150846668-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001145805.2(IRGM):​c.-968A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.206 in 151,786 control chromosomes in the GnomAD database, including 5,184 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.21 (5183 hom., cov: 32)
  • Exomes 𝑓: 0.047 (1 hom.)
• Consequence: IRGM NM_001145805.2 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.34

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]

IRGM (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.436 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IRGM	NM_001145805.2	c.-968A>G		5_prime_UTR_variant	1/2	ENST00000522154.2	NP_001139277.1
IRGM	NM_001346557.2	c.-968A>G		5_prime_UTR_variant	1/4		NP_001333486.1
IRGM	NR_170598.1	n.148A>G		non_coding_transcript_exon_variant	1/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IRGM	ENST00000522154	c.-968A>G		5_prime_UTR_variant	1/2	1	NM_001145805.2	ENSP00000428220.1

Frequencies

GnomAD3 genomes AF: 0.206 AC: 31129 AN: 151430 Hom.: 5169 Cov.: 32

Gnomad AFR AF: 0.441

Gnomad AMI AF: 0.0341

Gnomad AMR AF: 0.154

Gnomad ASJ AF: 0.164

Gnomad EAS AF: 0.432

Gnomad SAS AF: 0.207

Gnomad FIN AF: 0.0809

Gnomad MID AF: 0.201

Gnomad NFE AF: 0.0812

Gnomad OTH AF: 0.209

GnomAD4 exome AF: 0.0466 AC: 11 AN: 236 Hom.: 1 Cov.: 0 AF XY: 0.0484 AC XY: 9 AN XY: 186

Gnomad4 AFR exome AF: 0.250

Gnomad4 ASJ exome AF: 0.250

Gnomad4 EAS exome AF: 0.200

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0300

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.206 AC: 31182 AN: 151550 Hom.: 5183 Cov.: 32 AF XY: 0.206 AC XY: 15255 AN XY: 74062

Gnomad4 AFR AF: 0.441

Gnomad4 AMR AF: 0.153

Gnomad4 ASJ AF: 0.164

Gnomad4 EAS AF: 0.433

Gnomad4 SAS AF: 0.206

Gnomad4 FIN AF: 0.0809

Gnomad4 NFE AF: 0.0812

Gnomad4 OTH AF: 0.211

Alfa AF: 0.148 Hom.: 308

Asia WGS AF: 0.321 AC: 1118 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	3.4
DANN	Benign	0.13

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs34156253; hg19: chr5-150226230;