rs2288550

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_000883.4(IMPDH1):c.987G>C(p.Leu329Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.168 in 1,613,462 control chromosomes in the GnomAD database, including 23,740 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. L329L) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.14 ( 1650 hom., cov: 31)

Exomes 𝑓: 0.17 ( 22090 hom. )

Consequence

IMPDH1
NM_000883.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 2.20

Publications

19 publications found

Variant links:

Genes affected

IMPDH1 (HGNC:6052): (inosine monophosphate dehydrogenase 1) The protein encoded by this gene acts as a homotetramer to regulate cell growth. The encoded protein is an enzyme that catalyzes the synthesis of xanthine monophosphate (XMP) from inosine-5'-monophosphate (IMP). This is the rate-limiting step in the de novo synthesis of guanine nucleotides. Defects in this gene are a cause of retinitis pigmentosa type 10 (RP10). Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2008]

IMPDH1 Gene-Disease associations (from GenCC):

inherited retinal dystrophy
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
Leber congenital amaurosis 11
Inheritance: AD Classification: DEFINITIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P
retinitis pigmentosa 10
Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
Leber congenital amaurosis
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
retinitis pigmentosa
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

IMPDH1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.42).

BP6

Variant 7-128398501-C-G is Benign according to our data. Variant chr7-128398501-C-G is described in ClinVar as Benign. ClinVar VariationId is 358876.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=2.2 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.206 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IMPDH1	NM_000883.4 link	c.987G>C	p.Leu329Leu	synonymous_variant	Exon 10 of 17	ENST00000338791.11	NP_000874.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IMPDH1	ENST00000338791.11 link	c.987G>C	p.Leu329Leu	synonymous_variant	Exon 10 of 17	2	NM_000883.4	ENSP00000345096.6

Frequencies

GnomAD3 genomes

AF:

0.142

AC:

21605

AN:

152056

Hom.:

1647

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0773

Gnomad AMI

AF:

0.0857

Gnomad AMR

AF:

0.113

Gnomad ASJ

AF:

0.124

Gnomad EAS

AF:

0.127

Gnomad SAS

AF:

0.216

Gnomad FIN

AF:

0.196

Gnomad MID

AF:

0.155

Gnomad NFE

AF:

0.177

Gnomad OTH

AF:

0.152

GnomAD2 exomes

AF:

0.157

AC:

39491

AN:

250902

AF XY:

0.165

show subpopulations

Gnomad AFR exome

AF:

0.0753

Gnomad AMR exome

AF:

0.0882

Gnomad ASJ exome

AF:

0.124

Gnomad EAS exome

AF:

0.134

Gnomad FIN exome

AF:

0.191

Gnomad NFE exome

AF:

0.173

Gnomad OTH exome

AF:

0.146

GnomAD4 exome

AF:

0.170

AC:

248985

AN:

1461288

Hom.:

22090

Cov.:

AF XY:

0.173

AC XY:

125537

AN XY:

726956

show subpopulations

African (AFR)

AF:

0.0765

AC:

2561

AN:

33470

American (AMR)

AF:

0.0895

AC:

4001

AN:

44712

Ashkenazi Jewish (ASJ)

AF:

0.124

AC:

3243

AN:

26132

East Asian (EAS)

AF:

0.128

AC:

5101

AN:

39698

South Asian (SAS)

AF:

0.226

AC:

19509

AN:

86238

European-Finnish (FIN)

AF:

0.187

AC:

9960

AN:

53276

Middle Eastern (MID)

AF:

0.134

AC:

767

AN:

5742

European-Non Finnish (NFE)

AF:

0.175

AC:

194093

AN:

1111656

Other (OTH)

AF:

0.162

AC:

9750

AN:

60364

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

10413

20826

31240

41653

52066

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6862

13724

20586

27448

34310

<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:

0.142

AC:

21618

AN:

152174

Hom.:

1650

Cov.:

AF XY:

0.144

AC XY:

10715

AN XY:

74382

show subpopulations

African (AFR)

AF:

0.0772

AC:

3206

AN:

41526

American (AMR)

AF:

0.113

AC:

1725

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.124

AC:

429

AN:

3472

East Asian (EAS)

AF:

0.127

AC:

659

AN:

5176

South Asian (SAS)

AF:

0.217

AC:

1048

AN:

4822

European-Finnish (FIN)

AF:

0.196

AC:

2079

AN:

10590

Middle Eastern (MID)

AF:

0.160

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.177

AC:

12018

AN:

67974

Other (OTH)

AF:

0.156

AC:

329

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

954

1909

2863

3818

4772

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

260

520

780

1040

1300

<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:

0.163

Hom.:

619

Bravo

AF:

0.129

Asia WGS

AF:

0.178

AC:

617

AN:

3478

EpiCase

AF:

0.167

EpiControl

AF:

0.164

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Leber congenital amaurosis 11

Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Retinal dystrophy

Benign:1

Oct 01, 2023

Dept Of Ophthalmology, Nagoya University

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:research

- -

Retinitis pigmentosa

Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.42

CADD

Benign

6.6

(source)

DANN

Benign

0.81

PhyloP100

2.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over