NM_000883.4:c.1575G>A

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_000883.4(IMPDH1):c.1575G>A(p.Ala525Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.264 in 1,613,136 control chromosomes in the GnomAD database, including 57,199 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.25 ( 5025 hom., cov: 31)

Exomes 𝑓: 0.27 ( 52174 hom. )

Consequence

IMPDH1
NM_000883.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -2.88

Publications

30 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 -16 ACMG points.

BP6

Variant 7-128394575-C-T is Benign according to our data. Variant chr7-128394575-C-T is described in ClinVar as Benign. ClinVar VariationId is 358873.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.345 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IMPDH1	NM_000883.4 link	c.1575G>A	p.Ala525Ala	synonymous_variant	Exon 15 of 17	ENST00000338791.11	NP_000874.2	P20839-6B3KRZ3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IMPDH1	ENST00000338791.11 link	c.1575G>A	p.Ala525Ala	synonymous_variant	Exon 15 of 17	2	NM_000883.4	ENSP00000345096.6		P20839-6

Frequencies

GnomAD3 genomes

AF:

0.254

AC:

38542

AN:

151806

Hom.:

5018

Cov.:

show subpopulations

Gnomad AFR

AF:

0.209

Gnomad AMI

AF:

0.253

Gnomad AMR

AF:

0.253

Gnomad ASJ

AF:

0.315

Gnomad EAS

AF:

0.359

Gnomad SAS

AF:

0.257

Gnomad FIN

AF:

0.320

Gnomad MID

AF:

0.139

Gnomad NFE

AF:

0.261

Gnomad OTH

AF:

0.252

GnomAD2 exomes

AF:

0.272

AC:

68180

AN:

251108

AF XY:

0.270

show subpopulations

Gnomad AFR exome

AF:

0.202

Gnomad AMR exome

AF:

0.272

Gnomad ASJ exome

AF:

0.311

Gnomad EAS exome

AF:

0.368

Gnomad FIN exome

AF:

0.325

Gnomad NFE exome

AF:

0.259

Gnomad OTH exome

AF:

0.265

GnomAD4 exome

AF:

0.265

AC:

387809

AN:

1461210

Hom.:

52174

Cov.:

AF XY:

0.265

AC XY:

192704

AN XY:

726924

show subpopulations

African (AFR)

AF:

0.200

AC:

6688

AN:

33470

American (AMR)

AF:

0.273

AC:

12194

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.310

AC:

8095

AN:

26132

East Asian (EAS)

AF:

0.351

AC:

13914

AN:

39696

South Asian (SAS)

AF:

0.249

AC:

21488

AN:

86252

European-Finnish (FIN)

AF:

0.322

AC:

17130

AN:

53156

Middle Eastern (MID)

AF:

0.206

AC:

1183

AN:

5734

European-Non Finnish (NFE)

AF:

0.262

AC:

291147

AN:

1111670

Other (OTH)

AF:

0.264

AC:

15970

AN:

60380

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

17388

34776

52163

69551

86939

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9944

19888

29832

39776

49720

<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:

0.254

AC:

38575

AN:

151926

Hom.:

5025

Cov.:

AF XY:

0.258

AC XY:

19123

AN XY:

74236

show subpopulations

African (AFR)

AF:

0.208

AC:

8639

AN:

41434

American (AMR)

AF:

0.254

AC:

3883

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.315

AC:

1093

AN:

3470

East Asian (EAS)

AF:

0.359

AC:

1842

AN:

5134

South Asian (SAS)

AF:

0.257

AC:

1235

AN:

4808

European-Finnish (FIN)

AF:

0.320

AC:

3376

AN:

10558

Middle Eastern (MID)

AF:

0.133

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.261

AC:

17700

AN:

67924

Other (OTH)

AF:

0.255

AC:

538

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1470

2940

4411

5881

7351

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

400

800

1200

1600

2000

<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:

0.241

Hom.:

3739

Bravo

AF:

0.248

Asia WGS

AF:

0.303

AC:

1057

AN:

3478

EpiCase

AF:

0.252

EpiControl

AF:

0.250

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

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

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

- -

Leber congenital amaurosis 11

Benign:1

Jan 12, 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 12, 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

-0.73

CADD

Benign

5.5

(source)

DANN

Benign

0.54

PhyloP100

-2.9

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.33

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.33

Position offset: -25

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