rs72624912

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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. Variant has been reported in ClinVar as (no stars).

• 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
• Publications: 3 publications found

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

Our verdict: Benign. The variant received -8 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000884.3. 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
	IMPDH2	NM_000884.3	MANE Select	c.910+26A>G		intron	N/A	NP_000875.2	P12268
	IMPDH2	NM_001410759.1		c.910+26A>G		intron	N/A	NP_001397688.1	H0Y4R1
	IMPDH2	NM_001410760.1		c.835+26A>G		intron	N/A	NP_001397689.1	A0A7I2YQK5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IMPDH2	ENST00000326739.9	TSL:1 MANE Select	c.910+26A>G		intron	N/A	ENSP00000321584.4	P12268
	ENSG00000290315	ENST00000703936.1		c.2950+26A>G		intron	N/A	ENSP00000515567.1	A0A994J749
	IMPDH2	ENST00000937815.1		c.1078+26A>G		intron	N/A	ENSP00000607874.1

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

GnomAD2 exomes AF: 0.0104 AC: 2611 AN: 251284 AF XY: 0.0103

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 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

African (AFR) AF: 0.000751 AC: 25 AN: 33296

American (AMR) AF: 0.00277 AC: 124 AN: 44706

Ashkenazi Jewish (ASJ) AF: 0.00222 AC: 58 AN: 26082

East Asian (EAS) AF: 0.00 AC: 0 AN: 39668

South Asian (SAS) AF: 0.00782 AC: 673 AN: 86056

European-Finnish (FIN) AF: 0.0524 AC: 2798 AN: 53416

Middle Eastern (MID) AF: 0.0115 AC: 66 AN: 5756

European-Non Finnish (NFE) AF: 0.00597 AC: 6586 AN: 1103484

Other (OTH) AF: 0.00636 AC: 382 AN: 60086

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

African (AFR) AF: 0.00108 AC: 45 AN: 41542

American (AMR) AF: 0.00275 AC: 42 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.000865 AC: 3 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00684 AC: 33 AN: 4822

European-Finnish (FIN) AF: 0.0598 AC: 635 AN: 10612

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.00641 AC: 436 AN: 68014

Other (OTH) AF: 0.00567 AC: 12 AN: 2116

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	6.0
DANN	Benign	0.32
PhyloP100		0.24
Mutation Taster		=100/0	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: rs72624912; hg19: chr3-49063926;