rs72639213

Variant names:

• chr3-49029162-A-C
• rs72639213
• NM_000884.3:c.98+91T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_000884.3(IMPDH2):​c.98+91T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00187 in 1,073,490 control chromosomes in the GnomAD database, including 25 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 0.0076 (11 hom., cov: 33)
  • Exomes 𝑓: 0.00092 (14 hom.)
• Consequence: IMPDH2 NM_000884.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.525
• Publications: 0 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00762 (1161/152284) while in subpopulation AFR AF = 0.0266 (1107/41556). AF 95% confidence interval is 0.0253. There are 11 homozygotes in GnomAd4. There are 539 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High AC in GnomAd4 at 1161 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IMPDH2	NM_000884.3	c.98+91T>G		intron_variant	Intron 1 of 13	ENST00000326739.9	NP_000875.2
IMPDH2	NM_001410759.1	c.98+91T>G		intron_variant	Intron 1 of 14		NP_001397688.1
IMPDH2	NM_001410760.1	c.98+91T>G		intron_variant	Intron 1 of 13		NP_001397689.1
IMPDH2	NM_001410761.1	c.98+91T>G		intron_variant	Intron 1 of 12		NP_001397690.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IMPDH2	ENST00000326739.9	c.98+91T>G		intron_variant	Intron 1 of 13	1	NM_000884.3	ENSP00000321584.4
ENSG00000290315	ENST00000703936.1	c.2139-356T>G		intron_variant	Intron 9 of 21			ENSP00000515567.1

Frequencies

GnomAD3 genomes AF: 0.00753 AC: 1146 AN: 152166 Hom.: 9 Cov.: 33

Gnomad AFR AF: 0.0263

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00209

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000176

Gnomad OTH AF: 0.00479

GnomAD2 exomes AF: 0.00162 AC: 235 AN: 144696 AF XY: 0.00107

Gnomad AFR exome AF: 0.0255

Gnomad AMR exome AF: 0.00101

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000874

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000917 AC: 845 AN: 921206 Hom.: 14 Cov.: 12 AF XY: 0.000785 AC XY: 371 AN XY: 472588

African (AFR) AF: 0.0286 AC: 643 AN: 22506

American (AMR) AF: 0.00154 AC: 54 AN: 35142

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22208

East Asian (EAS) AF: 0.00 AC: 0 AN: 33656

South Asian (SAS) AF: 0.000171 AC: 12 AN: 70054

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 38278

Middle Eastern (MID) AF: 0.00103 AC: 5 AN: 4838

European-Non Finnish (NFE) AF: 0.0000383 AC: 25 AN: 651986

Other (OTH) AF: 0.00249 AC: 106 AN: 42538

GnomAD4 genome AF: 0.00762 AC: 1161 AN: 152284 Hom.: 11 Cov.: 33 AF XY: 0.00724 AC XY: 539 AN XY: 74474

African (AFR) AF: 0.0266 AC: 1107 AN: 41556

American (AMR) AF: 0.00203 AC: 31 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

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

European-Non Finnish (NFE) AF: 0.000176 AC: 12 AN: 68018

Other (OTH) AF: 0.00474 AC: 10 AN: 2108

Alfa AF: 0.00562 Hom.: 2

Bravo AF: 0.00901

Asia WGS AF: 0.00693 AC: 24 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.1
DANN	Benign	0.53
PhyloP100		-0.53
PromoterAI		0.010	Neutral
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs72639213; hg19: chr3-49066595;