dbSNP rs72639219: ENSG00000290315:c.2139-706C>T (chr3-49029512-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000703936.1(ENSG00000290315):c.2139-706C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00512 in 697,674 control chromosomes in the GnomAD database, including 92 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 0.016 ( 64 hom., cov: 33)

Exomes 𝑓: 0.0021 ( 28 hom. )

Consequence

ENSG00000290315
ENST00000703936.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.334

Variant links:

Genes affected

ENSG00000290315 (HGNC:):

ENSG00000290315 links:

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]

IMPDH2 links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0521 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IMPDH2	NM_000884.3 link	c.-162C>T		upstream_gene_variant		ENST00000326739.9	NP_000875.2	P12268A0A384N6C2
QRICH1	NM_198880.3 link	c.*940C>T		downstream_gene_variant		ENST00000395443.7	NP_942581.1	Q2TAL8A1L3Z9

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
ENSG00000290315	ENST00000703936.1 link	c.2139-706C>T	intron_variant	Intron 9 of 21			ENSP00000515567.1	A0A994J749
IMPDH2	ENST00000326739.9 link	c.-162C>T	upstream_gene_variant		1	NM_000884.3	ENSP00000321584.4	P12268
QRICH1	ENST00000395443.7 link	c.*940C>T	downstream_gene_variant		1	NM_198880.3	ENSP00000378830.2	Q2TAL8

Frequencies

GnomAD3 genomes

AF:

0.0159

AC:

2420

AN:

152242

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0539

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0100

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000622

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.0105

GnomAD3 exomes

AF:

0.00369

AC:

465

AN:

125852

Hom.:

AF XY:

0.00308

AC XY:

213

AN XY:

69058

show subpopulations

Gnomad AFR exome

AF:

0.0589

Gnomad AMR exome

AF:

0.00386

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000196

Gnomad SAS exome

AF:

0.0000453

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000837

Gnomad OTH exome

AF:

0.00103

GnomAD4 exome

AF:

0.00209

AC:

1141

AN:

545314

Hom.:

Cov.:

AF XY:

0.00175

AC XY:

515

AN XY:

294814

show subpopulations

Gnomad4 AFR exome

AF:

0.0550

Gnomad4 AMR exome

AF:

0.00394

Gnomad4 ASJ exome

AF:

0.0000508

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000977

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000537

Gnomad4 OTH exome

AF:

0.00421

GnomAD4 genome

AF:

0.0159

AC:

2428

AN:

152360

Hom.:

Cov.:

AF XY:

0.0154

AC XY:

1144

AN XY:

74498

show subpopulations

Gnomad4 AFR

AF:

0.0539

Gnomad4 AMR

AF:

0.00999

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000622

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.0104

Alfa

AF:

0.00630

Hom.:

Bravo

AF:

0.0185

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

1.1

DANN

Benign

0.92

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over