rs9637876

Variant names:

• chr5-150847863-C-T
• rs9637876
• NM_001145805.2:c.-261C>T

Variant summary

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

The NM_001145805.2(IRGM):​c.-261C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.143 in 421,450 control chromosomes in the GnomAD database, including 6,606 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 0.17 (2972 hom., cov: 32)
  • Exomes 𝑓: 0.13 (3634 hom.)
• Consequence: IRGM NM_001145805.2 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.299
• Publications: 25 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.418 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.-261C>T		5_prime_UTR	Exon 2 of 2	NP_001139277.1	A1A4Y4-1
	IRGM	NM_001346557.2		c.-261C>T		5_prime_UTR	Exon 2 of 4	NP_001333486.1	A1A4Y4-2
	IRGM	NR_170598.1		n.855C>T		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.-261C>T		5_prime_UTR	Exon 2 of 2	ENSP00000428220.1	A1A4Y4-1
	IRGM	ENST00000951736.1		c.-261C>T		5_prime_UTR	Exon 2 of 2	ENSP00000621795.1

Frequencies

GnomAD3 genomes AF: 0.166 AC: 25219 AN: 151994 Hom.: 2973 Cov.: 32

Gnomad AFR AF: 0.299

Gnomad AMI AF: 0.0351

Gnomad AMR AF: 0.142

Gnomad ASJ AF: 0.163

Gnomad EAS AF: 0.432

Gnomad SAS AF: 0.206

Gnomad FIN AF: 0.0817

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.0815

Gnomad OTH AF: 0.178

GnomAD4 exome AF: 0.130 AC: 35093 AN: 269338 Hom.: 3634 Cov.: 0 AF XY: 0.134 AC XY: 19009 AN XY: 141710

African (AFR) AF: 0.310 AC: 2683 AN: 8642

American (AMR) AF: 0.134 AC: 1287 AN: 9570

Ashkenazi Jewish (ASJ) AF: 0.174 AC: 1457 AN: 8374

East Asian (EAS) AF: 0.395 AC: 6651 AN: 16826

South Asian (SAS) AF: 0.189 AC: 5765 AN: 30496

European-Finnish (FIN) AF: 0.0856 AC: 1241 AN: 14496

Middle Eastern (MID) AF: 0.214 AC: 257 AN: 1202

European-Non Finnish (NFE) AF: 0.0825 AC: 13543 AN: 164134

Other (OTH) AF: 0.142 AC: 2209 AN: 15598

GnomAD4 genome AF: 0.166 AC: 25237 AN: 152112 Hom.: 2972 Cov.: 32 AF XY: 0.167 AC XY: 12421 AN XY: 74362

African (AFR) AF: 0.299 AC: 12387 AN: 41446

American (AMR) AF: 0.142 AC: 2173 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.163 AC: 567 AN: 3468

East Asian (EAS) AF: 0.433 AC: 2244 AN: 5182

South Asian (SAS) AF: 0.205 AC: 987 AN: 4814

European-Finnish (FIN) AF: 0.0817 AC: 866 AN: 10596

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

European-Non Finnish (NFE) AF: 0.0815 AC: 5543 AN: 68002

Other (OTH) AF: 0.179 AC: 377 AN: 2108

Alfa AF: 0.120 Hom.: 210

Bravo AF: 0.178

Asia WGS AF: 0.303 AC: 1053 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.0
DANN	Benign	0.55
PhyloP100		-0.30
Mutation Taster		=299/1	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: rs9637876; hg19: chr5-150227425;