rs11706052

Variant names:

• chr3-49026677-A-G
• rs11706052
• NM_000884.3:c.819+10T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000884.3(IMPDH2):​c.819+10T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0969 in 1,613,738 control chromosomes in the GnomAD database, including 8,215 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.076 (575 hom., cov: 33)
  • Exomes 𝑓: 0.099 (7640 hom.)
• Consequence: IMPDH2 NM_000884.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.998
• Publications: 59 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 3-49026677-A-G is Benign according to our data. Variant chr3-49026677-A-G is described in ClinVar as Benign. ClinVar VariationId is 1229935.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.103 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IMPDH2	NM_000884.3	MANE Select	c.819+10T>C		intron	N/A	NP_000875.2
	IMPDH2	NM_001410759.1		c.819+10T>C		intron	N/A	NP_001397688.1
	IMPDH2	NM_001410760.1		c.744+10T>C		intron	N/A	NP_001397689.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IMPDH2	ENST00000326739.9	TSL:1 MANE Select	c.819+10T>C		intron	N/A	ENSP00000321584.4
	ENSG00000290315	ENST00000703936.1		c.2859+10T>C		intron	N/A	ENSP00000515567.1
	IMPDH2	ENST00000677108.1		n.2735T>C		non_coding_transcript_exon	Exon 1 of 4

Frequencies

GnomAD3 genomes AF: 0.0757 AC: 11511 AN: 152158 Hom.: 575 Cov.: 33

Gnomad AFR AF: 0.0221

Gnomad AMI AF: 0.0866

Gnomad AMR AF: 0.0706

Gnomad ASJ AF: 0.123

Gnomad EAS AF: 0.0379

Gnomad SAS AF: 0.0605

Gnomad FIN AF: 0.114

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.105

Gnomad OTH AF: 0.0824

GnomAD2 exomes AF: 0.0834 AC: 20969 AN: 251340 AF XY: 0.0840

Gnomad AFR exome AF: 0.0205

Gnomad AMR exome AF: 0.0481

Gnomad ASJ exome AF: 0.121

Gnomad EAS exome AF: 0.0379

Gnomad FIN exome AF: 0.117

Gnomad NFE exome AF: 0.107

Gnomad OTH exome AF: 0.0933

GnomAD4 exome AF: 0.0991 AC: 144841 AN: 1461460 Hom.: 7640 Cov.: 33 AF XY: 0.0979 AC XY: 71177 AN XY: 727058

African (AFR) AF: 0.0182 AC: 609 AN: 33478

American (AMR) AF: 0.0510 AC: 2280 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.118 AC: 3077 AN: 26134

East Asian (EAS) AF: 0.0424 AC: 1684 AN: 39698

South Asian (SAS) AF: 0.0578 AC: 4982 AN: 86252

European-Finnish (FIN) AF: 0.119 AC: 6321 AN: 53310

Middle Eastern (MID) AF: 0.0756 AC: 436 AN: 5768

European-Non Finnish (NFE) AF: 0.108 AC: 119967 AN: 1111720

Other (OTH) AF: 0.0908 AC: 5485 AN: 60380

GnomAD4 genome AF: 0.0756 AC: 11512 AN: 152278 Hom.: 575 Cov.: 33 AF XY: 0.0760 AC XY: 5657 AN XY: 74446

African (AFR) AF: 0.0220 AC: 914 AN: 41568

American (AMR) AF: 0.0706 AC: 1080 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.123 AC: 428 AN: 3472

East Asian (EAS) AF: 0.0382 AC: 198 AN: 5184

South Asian (SAS) AF: 0.0606 AC: 292 AN: 4822

European-Finnish (FIN) AF: 0.114 AC: 1208 AN: 10606

Middle Eastern (MID) AF: 0.102 AC: 30 AN: 294

European-Non Finnish (NFE) AF: 0.105 AC: 7110 AN: 68010

Other (OTH) AF: 0.0819 AC: 173 AN: 2112

Alfa AF: 0.0925 Hom.: 2170

Bravo AF: 0.0694

Asia WGS AF: 0.0540 AC: 190 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	IMPDH2-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	1.4
DANN	Benign	0.61
PhyloP100		-1.0
Mutation Taster		=100/0	polymorphism (auto)

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: rs11706052; hg19: chr3-49064110; COSMIC: COSV58707418; COSMIC: COSV58707418;