5-150846701-G-A

Variant names:

• chr5-150846701-G-A
• rs61270113
• NM_001145805.2:c.-935G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001145805.2(IRGM):​c.-935G>A 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 152,054 control chromosomes in the GnomAD database, including 5,175 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 (5175 hom., cov: 32)
  • Exomes 𝑓: 0.050 (0 hom.)
• Consequence: IRGM NM_001145805.2 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.146
• Publications: 6 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.435 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IRGM	NM_001145805.2	MANE Select	c.-935G>A		5_prime_UTR	Exon 1 of 2	NP_001139277.1
	IRGM	NR_170598.1		n.181G>A		non_coding_transcript_exon	Exon 1 of 5
	IRGM	NM_001346557.2		c.-935G>A		5_prime_UTR	Exon 1 of 4	NP_001333486.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IRGM	ENST00000522154.2	TSL:1 MANE Select	c.-935G>A		5_prime_UTR	Exon 1 of 2	ENSP00000428220.1
	IRGM	ENST00000609660.1	TSL:6	n.-102G>A		upstream_gene	N/A

Frequencies

GnomAD3 genomes AF: 0.206 AC: 31210 AN: 151612 Hom.: 5161 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: 0.210

Gnomad FIN AF: 0.0811

Gnomad MID AF: 0.204

Gnomad NFE AF: 0.0816

Gnomad OTH AF: 0.208

GnomAD4 exome AF: 0.0497 AC: 16 AN: 322 Hom.: 0 Cov.: 0 AF XY: 0.0444 AC XY: 11 AN XY: 248

African (AFR) AF: 0.250 AC: 2 AN: 8

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AF: 0.500 AC: 1 AN: 2

East Asian (EAS) AF: 0.0833 AC: 1 AN: 12

South Asian (SAS) AF: 0.00 AC: 0 AN: 6

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8

Middle Eastern (MID) AF: 0.500 AC: 1 AN: 2

European-Non Finnish (NFE) AF: 0.0292 AC: 8 AN: 274

Other (OTH) AF: 0.300 AC: 3 AN: 10

GnomAD4 genome AF: 0.206 AC: 31262 AN: 151732 Hom.: 5175 Cov.: 32 AF XY: 0.206 AC XY: 15298 AN XY: 74188

African (AFR) AF: 0.441 AC: 18185 AN: 41258

American (AMR) AF: 0.154 AC: 2346 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.164 AC: 568 AN: 3464

East Asian (EAS) AF: 0.433 AC: 2222 AN: 5136

South Asian (SAS) AF: 0.209 AC: 1002 AN: 4802

European-Finnish (FIN) AF: 0.0811 AC: 857 AN: 10568

Middle Eastern (MID) AF: 0.207 AC: 61 AN: 294

European-Non Finnish (NFE) AF: 0.0816 AC: 5548 AN: 67952

Other (OTH) AF: 0.210 AC: 442 AN: 2104

Alfa AF: 0.0498 Hom.: 90

Bravo AF: 0.224

Asia WGS AF: 0.321 AC: 1117 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	6.3
DANN	Benign	0.34
PhyloP100		0.15
PromoterAI		0.030	Neutral
Mutation Taster		=300/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs61270113; hg19: chr5-150226263;