3-49029419-G-T

Variant names:

• chr3-49029419-G-T
• rs72624904
• ENST00000703936.1:c.2139-613C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000703936.1(ENSG00000290315):​c.2139-613C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000103 in 972,858 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000010 (0 hom.)
• Consequence: ENSG00000290315 ENST00000703936.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.23
• Publications: 0 publications found

Genes affected

ENSG00000290315 (HGNC:):

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.28).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IMPDH2	NM_000884.3	c.-69C>A		upstream_gene_variant		ENST00000326739.9	NP_000875.2
IMPDH2	NM_001410759.1	c.-69C>A		upstream_gene_variant			NP_001397688.1
IMPDH2	NM_001410760.1	c.-69C>A		upstream_gene_variant			NP_001397689.1
IMPDH2	NM_001410761.1	c.-69C>A		upstream_gene_variant			NP_001397690.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000290315	ENST00000703936.1	c.2139-613C>A		intron_variant	Intron 9 of 21			ENSP00000515567.1
IMPDH2	ENST00000326739.9	c.-69C>A		upstream_gene_variant		1	NM_000884.3	ENSP00000321584.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000103 AC: 1 AN: 972858 Hom.: 0 Cov.: 13 AF XY: 0.00000201 AC XY: 1 AN XY: 496772

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 23414

American (AMR) AF: 0.00 AC: 0 AN: 35180

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22614

East Asian (EAS) AF: 0.00 AC: 0 AN: 33920

South Asian (SAS) AF: 0.00 AC: 0 AN: 70898

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 41550

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4926

European-Non Finnish (NFE) AF: 0.00000144 AC: 1 AN: 696242

Other (OTH) AF: 0.00 AC: 0 AN: 44114

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.28
CADD	Benign	20
DANN	Benign	0.94
PhyloP100		1.2
PromoterAI		0.037	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs72624904; hg19: chr3-49066852;