rs72624903

Variant names:

• chr3-49029468-G-A
• rs72624903
• ENST00000703936.1:c.2139-662C>T

Your query was ambiguous. Multiple possible variants found:

• chr3-49029468-G-A
• chr3-49029468-G-C

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The ENST00000703936.1(ENSG00000290315):​c.2139-662C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000585 in 810,594 control chromosomes in the GnomAD database, including 4 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 0.00048 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00061 (4 hom.)
• Consequence: ENSG00000290315 ENST00000703936.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.650
• 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]

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: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).
• BS2: High Homozygotes in GnomAdExome4 at 4 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IMPDH2	NM_000884.3	c.-118C>T		upstream_gene_variant		ENST00000326739.9	NP_000875.2
QRICH1	NM_198880.3	c.*984C>T		downstream_gene_variant		ENST00000395443.7	NP_942581.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000290315	ENST00000703936.1	c.2139-662C>T		intron_variant	Intron 9 of 21			ENSP00000515567.1
IMPDH2	ENST00000326739.9	c.-118C>T		upstream_gene_variant		1	NM_000884.3	ENSP00000321584.4
QRICH1	ENST00000395443.7	c.*984C>T		downstream_gene_variant		1	NM_198880.3	ENSP00000378830.2

Frequencies

GnomAD3 genomes AF: 0.000473 AC: 72 AN: 152250 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0125

Gnomad SAS AF: 0.00103

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00143 AC: 189 AN: 132342 AF XY: 0.00143

Gnomad AFR exome AF: 0.000152

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0152

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000199

Gnomad OTH exome AF: 0.000245

GnomAD4 exome AF: 0.000609 AC: 401 AN: 658226 Hom.: 4 Cov.: 8 AF XY: 0.000586 AC XY: 205 AN XY: 349664

African (AFR) AF: 0.0000565 AC: 1 AN: 17698

American (AMR) AF: 0.00 AC: 0 AN: 34756

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20624

East Asian (EAS) AF: 0.00963 AC: 313 AN: 32492

South Asian (SAS) AF: 0.00114 AC: 73 AN: 64270

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34390

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4284

European-Non Finnish (NFE) AF: 0.0000168 AC: 7 AN: 415574

Other (OTH) AF: 0.000205 AC: 7 AN: 34138

GnomAD4 genome AF: 0.000479 AC: 73 AN: 152368 Hom.: 0 Cov.: 33 AF XY: 0.000590 AC XY: 44 AN XY: 74518

African (AFR) AF: 0.00 AC: 0 AN: 41598

American (AMR) AF: 0.0000653 AC: 1 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.0127 AC: 66 AN: 5186

South Asian (SAS) AF: 0.00103 AC: 5 AN: 4832

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

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68026

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.0000693 Hom.: 0

Bravo AF: 0.000744

Asia WGS AF: 0.00520 AC: 18 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	16
DANN	Benign	0.91
PhyloP100		0.65
PromoterAI		-0.27	Neutral

Splicing

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

Other links and lift over

dbSNP: rs72624903; hg19: chr3-49066901;