rs2288550

Positions:

Variant summary

Our verdict is Benign. Variant got -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 (★★).

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

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id is 358876.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-128398501-C-G is described in Lovd as [Benign].

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/exons	MANE	Protein	UniProt
IMPDH1	NM_000883.4 link	c.987G>C	p.Leu329Leu	synonymous_variant	10/17	ENST00000338791.11	NP_000874.2	P20839-6B3KRZ3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IMPDH1	ENST00000338791.11 link	c.987G>C	p.Leu329Leu	synonymous_variant	10/17	2	NM_000883.4	ENSP00000345096.6		P20839-6

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

GnomAD3 exomes

AF:

0.157

AC:

39491

AN:

250902

Hom.:

3373

AF XY:

0.165

AC XY:

22338

AN XY:

135668

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 SAS exome

AF:

0.226

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

Gnomad4 AFR exome

AF:

0.0765

Gnomad4 AMR exome

AF:

0.0895

Gnomad4 ASJ exome

AF:

0.124

Gnomad4 EAS exome

AF:

0.128

Gnomad4 SAS exome

AF:

0.226

Gnomad4 FIN exome

AF:

0.187

Gnomad4 NFE exome

AF:

0.175

Gnomad4 OTH exome

AF:

0.162

GnomAD4 genome

AF:

0.142

AC:

21618

AN:

152174

Hom.:

1650

Cov.:

AF XY:

0.144

AC XY:

10715

AN XY:

74382

show subpopulations

Gnomad4 AFR

AF:

0.0772

Gnomad4 AMR

AF:

0.113

Gnomad4 ASJ

AF:

0.124

Gnomad4 EAS

AF:

0.127

Gnomad4 SAS

AF:

0.217

Gnomad4 FIN

AF:

0.196

Gnomad4 NFE

AF:

0.177

Gnomad4 OTH

AF:

0.156

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

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 03, 2025	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -

Leber congenital amaurosis 11

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

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

Benign, criteria provided, single submitter

research

Dept Of Ophthalmology, Nagoya University

Oct 01, 2023

- -

Retinitis pigmentosa

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.42

CADD

Benign

6.6

DANN

Benign

0.81

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over