Genetic Variant ENST00000703936.1:c.2139-706C>T (chr3-49029512-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -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

Publications

1 publications found

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 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)

QRICH1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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

GnomAD2 exomes

AF:

0.00369

AC:

465

AN:

125852

AF XY:

0.00308

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 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

African (AFR)

AF:

0.0550

AC:

851

AN:

15464

American (AMR)

AF:

0.00394

AC:

130

AN:

33030

Ashkenazi Jewish (ASJ)

AF:

0.0000508

AC:

AN:

19686

East Asian (EAS)

AF:

0.00

AC:

AN:

31862

South Asian (SAS)

AF:

0.0000977

AC:

AN:

61430

European-Finnish (FIN)

AF:

0.00

AC:

AN:

32916

Middle Eastern (MID)

AF:

0.00223

AC:

AN:

4036

European-Non Finnish (NFE)

AF:

0.0000537

AC:

AN:

316728

Other (OTH)

AF:

0.00421

AC:

127

AN:

30162

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

120

180

240

300

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0159

AC:

2428

AN:

152360

Hom.:

Cov.:

AF XY:

0.0154

AC XY:

1144

AN XY:

74498

show subpopulations

African (AFR)

AF:

0.0539

AC:

2243

AN:

41580

American (AMR)

AF:

0.00999

AC:

153

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.000622

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000588

AC:

AN:

68040

Other (OTH)

AF:

0.0104

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

122

245

367

490

612

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

110

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00722

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

(source)

DANN

Benign

0.92

PhyloP100

-0.33

PromoterAI

-0.067

Neutral

(source)

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over