3-49029624-G-T

Variant names:

• chr3-49029624-G-T
• rs72639217
• ENST00000703936.1:c.2139-818C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000703936.1(ENSG00000290315):​c.2139-818C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000807 in 371,654 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: 33)
  • Exomes 𝑓: 0.0000081 (0 hom.)
• Consequence: ENSG00000290315 ENST00000703936.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00400
• Publications: 1 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]

QRICH1 (HGNC:24713): (glutamine rich 1) Enables DNA binding activity. Involved in several processes, including PERK-mediated unfolded protein response; intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress; and positive regulation of transcription, DNA-templated. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

QRICH1 Gene-Disease associations (from GenCC):

• syndromic intellectual disability

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• Ververi-Brady syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae), Illumina
• schizophrenia

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000703936.1. 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.-274C>A		upstream_gene	N/A	NP_000875.2
	QRICH1	NM_198880.3	MANE Select	c.*828C>A		downstream_gene	N/A	NP_942581.1
	IMPDH2	NM_001410759.1		c.-274C>A		upstream_gene	N/A	NP_001397688.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000290315	ENST00000703936.1		c.2139-818C>A		intron	N/A	ENSP00000515567.1
	ENSG00000272434	ENST00000607245.1	TSL:6	n.309G>T		non_coding_transcript_exon	Exon 1 of 1
	ENSG00000290315	ENST00000703937.1		n.*828C>A		non_coding_transcript_exon	Exon 12 of 25	ENSP00000515568.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000807 AC: 3 AN: 371654 Hom.: 0 Cov.: 0 AF XY: 0.00000511 AC XY: 1 AN XY: 195666

African (AFR) AF: 0.00 AC: 0 AN: 10912

American (AMR) AF: 0.00 AC: 0 AN: 14924

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 11526

East Asian (EAS) AF: 0.00 AC: 0 AN: 24214

South Asian (SAS) AF: 0.00 AC: 0 AN: 44844

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 22472

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1940

European-Non Finnish (NFE) AF: 0.0000137 AC: 3 AN: 219268

Other (OTH) AF: 0.00 AC: 0 AN: 21554

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.91
DANN	Benign	0.75
PhyloP100		0.0040
PromoterAI		-0.012	Neutral

Splicing

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

Other links and lift over

dbSNP: rs72639217; hg19: chr3-49067057;