rs72639217

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr3-49029624-G-A
• chr3-49029624-G-T

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>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000227 in 523,886 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: 𝑓 0.00016 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00026 (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 complex neurodevelopmental disorder

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• Ververi-Brady syndrome 1

  Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), Illumina, G2P
• 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=-0.8).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IMPDH2	NM_000884.3	MANE Select	c.-274C>T		upstream_gene	N/A	NP_000875.2	P12268
	QRICH1	NM_198880.3	MANE Select	c.*828C>T		downstream_gene	N/A	NP_942581.1	A1L3Z9
	IMPDH2	NM_001410759.1		c.-274C>T		upstream_gene	N/A	NP_001397688.1	H0Y4R1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000290315	ENST00000703936.1		c.2139-818C>T		intron	N/A	ENSP00000515567.1	A0A994J749
	ENSG00000272434	ENST00000607245.1	TSL:6	n.309G>A		non_coding_transcript_exon	Exon 1 of 1
	ENSG00000290315	ENST00000703937.1		n.*828C>T		non_coding_transcript_exon	Exon 12 of 25	ENSP00000515568.1	A0A994J420

Frequencies

GnomAD3 genomes AF: 0.000158 AC: 24 AN: 152234 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00317

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000162

Gnomad OTH AF: 0.000956

GnomAD4 exome AF: 0.000256 AC: 95 AN: 371652 Hom.: 0 Cov.: 0 AF XY: 0.000281 AC XY: 55 AN XY: 195666

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

American (AMR) AF: 0.0000670 AC: 1 AN: 14922

Ashkenazi Jewish (ASJ) AF: 0.00495 AC: 57 AN: 11526

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

South Asian (SAS) AF: 0.0000223 AC: 1 AN: 44844

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

Middle Eastern (MID) AF: 0.000515 AC: 1 AN: 1940

European-Non Finnish (NFE) AF: 0.000137 AC: 30 AN: 219268

Other (OTH) AF: 0.000232 AC: 5 AN: 21554

GnomAD4 genome AF: 0.000158 AC: 24 AN: 152234 Hom.: 0 Cov.: 33 AF XY: 0.000161 AC XY: 12 AN XY: 74384

African (AFR) AF: 0.00 AC: 0 AN: 41464

American (AMR) AF: 0.00 AC: 0 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.00317 AC: 11 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5202

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000162 AC: 11 AN: 68046

Other (OTH) AF: 0.000956 AC: 2 AN: 2092

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.000193

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	1.1
DANN	Benign	0.79
PhyloP100		0.0040
PromoterAI		-0.041	Neutral

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs72639217;

hg19: chr3-49067057;