rs72624912

Variant names:

• chr3-49026493-T-C
• rs72624912
• NM_000884.3:c.910+26A>G

Variant summary

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

The NM_000884.3(IMPDH2):​c.910+26A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00743 in 1,604,814 control chromosomes in the GnomAD database, including 139 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 0.0079 (20 hom., cov: 32)
  • Exomes 𝑓: 0.0074 (119 hom.)
• Consequence: IMPDH2 NM_000884.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.237

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]

ENSG00000290315 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BS2: High AC in GnomAd4 at 1208 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IMPDH2	NM_000884.3	c.910+26A>G		intron_variant	Intron 8 of 13	ENST00000326739.9	NP_000875.2
IMPDH2	NM_001410759.1	c.910+26A>G		intron_variant	Intron 8 of 14		NP_001397688.1
IMPDH2	NM_001410760.1	c.835+26A>G		intron_variant	Intron 7 of 13		NP_001397689.1
IMPDH2	NM_001410761.1	c.835+26A>G		intron_variant	Intron 7 of 12		NP_001397690.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IMPDH2	ENST00000326739.9	c.910+26A>G		intron_variant	Intron 8 of 13	1	NM_000884.3	ENSP00000321584.4
ENSG00000290315	ENST00000703936.1	c.2950+26A>G		intron_variant	Intron 16 of 21			ENSP00000515567.1

Frequencies

GnomAD3 genomes AF: 0.00795 AC: 1209 AN: 152146 Hom.: 20 Cov.: 32

Gnomad AFR AF: 0.00109

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.00275

Gnomad ASJ AF: 0.000865

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00663

Gnomad FIN AF: 0.0598

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00642

Gnomad OTH AF: 0.00573

GnomAD3 exomes AF: 0.0104 AC: 2611 AN: 251284 Hom.: 50 AF XY: 0.0103 AC XY: 1395 AN XY: 135846

Gnomad AFR exome AF: 0.000985

Gnomad AMR exome AF: 0.00263

Gnomad ASJ exome AF: 0.00218

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.00758

Gnomad FIN exome AF: 0.0596

Gnomad NFE exome AF: 0.00794

Gnomad OTH exome AF: 0.00930

GnomAD4 exome AF: 0.00737 AC: 10712 AN: 1452550 Hom.: 119 Cov.: 28 AF XY: 0.00723 AC XY: 5227 AN XY: 723290

Gnomad4 AFR exome AF: 0.000751

Gnomad4 AMR exome AF: 0.00277

Gnomad4 ASJ exome AF: 0.00222

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00782

Gnomad4 FIN exome AF: 0.0524

Gnomad4 NFE exome AF: 0.00597

Gnomad4 OTH exome AF: 0.00636

GnomAD4 genome AF: 0.00793 AC: 1208 AN: 152264 Hom.: 20 Cov.: 32 AF XY: 0.0104 AC XY: 773 AN XY: 74458

Gnomad4 AFR AF: 0.00108

Gnomad4 AMR AF: 0.00275

Gnomad4 ASJ AF: 0.000865

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00684

Gnomad4 FIN AF: 0.0598

Gnomad4 NFE AF: 0.00641

Gnomad4 OTH AF: 0.00567

Alfa AF: 0.00585 Hom.: 0

Bravo AF: 0.00365

Asia WGS AF: 0.00173 AC: 8 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	6.0
DANN	Benign	0.32

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: rs72624912; hg19: chr3-49063926;