rs72624917

chr3-49024852-G-Achr3-49024852-G-C

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_000884.3(IMPDH2):c.1295+44C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00461 in 1,614,160 control chromosomes in the GnomAD database, including 22 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 0.0030 (2 hom., cov: 33)
  • Exomes 𝑓: 0.0048 (20 hom.)
• Consequence: IMPDH2 NM_000884.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.220

Genes affected

IMPDH2 (HGNC:6053): (inosine monophosphate dehydrogenase 2) This gene encodes the rate-limiting enzyme in the de novo guanine nucleotide biosynthesis. It is thus involved in maintaining cellular guanine deoxy- and ribonucleotide pools needed for DNA and RNA synthesis. The encoded protein catalyzes the NAD-dependent oxidation of inosine-5'-monophosphate into xanthine-5'-monophosphate, which is then converted into guanosine-5'-monophosphate. This gene is up-regulated in some neoplasms, suggesting it may play a role in malignant transformation. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BS2: High AC in GnomAd at 461 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IMPDH2	NM_000884.3	c.1295+44C>T		intron_variant		ENST00000326739.9
IMPDH2	NM_001410759.1	c.1367+44C>T		intron_variant
IMPDH2	NM_001410760.1	c.1292+44C>T		intron_variant
IMPDH2	NM_001410761.1	c.1220+44C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IMPDH2	ENST00000326739.9	c.1295+44C>T		intron_variant		1	NM_000884.3	P1

Frequencies

GnomAD3 genomes AF: 0.00303 AC: 461 AN: 152248 Hom.: 2 Cov.: 33

Gnomad AFR AF: 0.00166

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00386

Gnomad ASJ AF: 0.00346

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.000471

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00444

Gnomad OTH AF: 0.00525

GnomAD3 exomes AF: 0.00294 AC: 739 AN: 251248 Hom.: 1 AF XY: 0.00289 AC XY: 393 AN XY: 135786

Gnomad AFR exome AF: 0.000984

Gnomad AMR exome AF: 0.00362

Gnomad ASJ exome AF: 0.00427

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000163

Gnomad FIN exome AF: 0.000555

Gnomad NFE exome AF: 0.00453

Gnomad OTH exome AF: 0.00375

GnomAD4 exome AF: 0.00477 AC: 6974 AN: 1461794 Hom.: 20 Cov.: 33 AF XY: 0.00463 AC XY: 3368 AN XY: 727200

Gnomad4 AFR exome AF: 0.000866

Gnomad4 AMR exome AF: 0.00405

Gnomad4 ASJ exome AF: 0.00398

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000243

Gnomad4 FIN exome AF: 0.000468

Gnomad4 NFE exome AF: 0.00573

Gnomad4 OTH exome AF: 0.00391

GnomAD4 genome AF: 0.00303 AC: 461 AN: 152366 Hom.: 2 Cov.: 33 AF XY: 0.00276 AC XY: 206 AN XY: 74506

Gnomad4 AFR AF: 0.00166

Gnomad4 AMR AF: 0.00385

Gnomad4 ASJ AF: 0.00346

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.000471

Gnomad4 NFE AF: 0.00444

Gnomad4 OTH AF: 0.00520

Alfa AF: 0.00157 Hom.: 0

Bravo AF: 0.00346

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	0.40
Dann	Benign	0.59

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: rs72624917; hg19: chr3-49062285;