chr3-49027143-C-T

Variant names:

• chr3-49027143-C-T
• rs72624911
• NM_000884.3:c.532-96G>A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_000884.3(IMPDH2):​c.532-96G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0395 in 904,786 control chromosomes in the GnomAD database, including 938 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 0.031 (105 hom., cov: 33)
  • Exomes 𝑓: 0.041 (833 hom.)
• Consequence: IMPDH2 NM_000884.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.357

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0315 (4789/152198) while in subpopulation NFE AF= 0.0476 (3234/68012). AF 95% confidence interval is 0.0462. There are 105 homozygotes in gnomad4. There are 2324 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 4789 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IMPDH2	NM_000884.3	c.532-96G>A		intron_variant	Intron 5 of 13	ENST00000326739.9	NP_000875.2
IMPDH2	NM_001410759.1	c.532-96G>A		intron_variant	Intron 5 of 14		NP_001397688.1
IMPDH2	NM_001410760.1	c.457-96G>A		intron_variant	Intron 4 of 13		NP_001397689.1
IMPDH2	NM_001410761.1	c.457-96G>A		intron_variant	Intron 4 of 12		NP_001397690.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IMPDH2	ENST00000326739.9	c.532-96G>A		intron_variant	Intron 5 of 13	1	NM_000884.3	ENSP00000321584.4
ENSG00000290315	ENST00000703936.1	c.2572-96G>A		intron_variant	Intron 13 of 21			ENSP00000515567.1

Frequencies

GnomAD3 genomes AF: 0.0315 AC: 4790 AN: 152080 Hom.: 105 Cov.: 33

Gnomad AFR AF: 0.00753

Gnomad AMI AF: 0.0384

Gnomad AMR AF: 0.0156

Gnomad ASJ AF: 0.0672

Gnomad EAS AF: 0.00231

Gnomad SAS AF: 0.0414

Gnomad FIN AF: 0.0450

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0475

Gnomad OTH AF: 0.0226

GnomAD4 exome AF: 0.0411 AC: 30916 AN: 752588 Hom.: 833 AF XY: 0.0421 AC XY: 16870 AN XY: 400322

Gnomad4 AFR exome AF: 0.00670

Gnomad4 AMR exome AF: 0.0115

Gnomad4 ASJ exome AF: 0.0704

Gnomad4 EAS exome AF: 0.000934

Gnomad4 SAS exome AF: 0.0473

Gnomad4 FIN exome AF: 0.0406

Gnomad4 NFE exome AF: 0.0463

Gnomad4 OTH exome AF: 0.0395

GnomAD4 genome AF: 0.0315 AC: 4789 AN: 152198 Hom.: 105 Cov.: 33 AF XY: 0.0312 AC XY: 2324 AN XY: 74404

Gnomad4 AFR AF: 0.00751

Gnomad4 AMR AF: 0.0156

Gnomad4 ASJ AF: 0.0672

Gnomad4 EAS AF: 0.00232

Gnomad4 SAS AF: 0.0413

Gnomad4 FIN AF: 0.0450

Gnomad4 NFE AF: 0.0476

Gnomad4 OTH AF: 0.0223

Alfa AF: 0.0398 Hom.: 21

Bravo AF: 0.0267

Asia WGS AF: 0.0170 AC: 62 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.84
DANN	Benign	0.55
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs72624911; hg19: chr3-49064576;