7-128395076-ACC-AC

Variant names:

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_000883.4(IMPDH1):c.1406-44delG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0368 in 1,612,738 control chromosomes in the GnomAD database, including 2,258 homozygotes. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.035 ( 219 hom., cov: 32)

Exomes 𝑓: 0.037 ( 2039 hom. )

Consequence

IMPDH1
NM_000883.4 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.188

Publications

1 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):

IMPDH1-related retinopathy
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, Labcorp Genetics (formerly Invitae), G2P
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

new If you want to explore the variant's impact on the transcript NM_000883.4, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP6

Variant 7-128395076-AC-A is Benign according to our data. Variant chr7-128395076-AC-A is described in ClinVar as Benign. ClinVar VariationId is 1259283.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.2 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000883.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
IMPDH1	NM_000883.4	MANE Select	c.1406-44delG	intron	N/A	NP_000874.2
IMPDH1	NM_001102605.2		c.1376-44delG	intron	N/A	NP_001096075.1	P20839-5
IMPDH1	NM_001142576.2		c.1307-44delG	intron	N/A	NP_001136048.1	P20839-7

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
IMPDH1	ENST00000338791.11	TSL:2 MANE Select	c.1406-44delG	intron	N/A	ENSP00000345096.6	P20839-6
IMPDH1	ENST00000348127.11	TSL:1	c.1298-44delG	intron	N/A	ENSP00000265385.8	P20839-3
IMPDH1	ENST00000955327.1		c.1394-44delG	intron	N/A	ENSP00000625386.1

Frequencies

GnomAD3 genomes

AF:

0.0346

AC:

5240

AN:

151312

Hom.:

219

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0190

Gnomad AMI

AF:

0.00330

Gnomad AMR

AF:

0.0312

Gnomad ASJ

AF:

0.0673

Gnomad EAS

AF:

0.210

Gnomad SAS

AF:

0.137

Gnomad FIN

AF:

0.00771

Gnomad MID

AF:

0.0696

Gnomad NFE

AF:

0.0269

Gnomad OTH

AF:

0.0434

GnomAD2 exomes

AF:

0.0534

AC:

13365

AN:

250410

AF XY:

0.0566

show subpopulations

Gnomad AFR exome

AF:

0.0204

Gnomad AMR exome

AF:

0.0272

Gnomad ASJ exome

AF:

0.0628

Gnomad EAS exome

AF:

0.216

Gnomad FIN exome

AF:

0.00678

Gnomad NFE exome

AF:

0.0266

Gnomad OTH exome

AF:

0.0469

GnomAD4 exome

AF:

0.0371

AC:

54171

AN:

1461312

Hom.:

2039

Cov.:

AF XY:

0.0398

AC XY:

28909

AN XY:

726978

show subpopulations

African (AFR)

AF:

0.0188

AC:

630

AN:

33478

American (AMR)

AF:

0.0285

AC:

1274

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.0649

AC:

1697

AN:

26134

East Asian (EAS)

AF:

0.176

AC:

6998

AN:

39700

South Asian (SAS)

AF:

0.127

AC:

10929

AN:

86254

European-Finnish (FIN)

AF:

0.00789

AC:

418

AN:

52962

Middle Eastern (MID)

AF:

0.0629

AC:

363

AN:

5768

European-Non Finnish (NFE)

AF:

0.0260

AC:

28919

AN:

1111912

Other (OTH)

AF:

0.0487

AC:

2943

AN:

60386

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

3627

7254

10881

14508

18135

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1274

2548

3822

5096

6370

<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:

0.0346

AC:

5233

AN:

151426

Hom.:

219

Cov.:

AF XY:

0.0365

AC XY:

2698

AN XY:

73952

show subpopulations

African (AFR)

AF:

0.0189

AC:

782

AN:

41268

American (AMR)

AF:

0.0312

AC:

474

AN:

15192

Ashkenazi Jewish (ASJ)

AF:

0.0673

AC:

233

AN:

3460

East Asian (EAS)

AF:

0.210

AC:

1075

AN:

5118

South Asian (SAS)

AF:

0.136

AC:

647

AN:

4760

European-Finnish (FIN)

AF:

0.00771

AC:

AN:

10512

Middle Eastern (MID)

AF:

0.0714

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0269

AC:

1826

AN:

67820

Other (OTH)

AF:

0.0435

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

251

502

754

1005

1256

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

140

210

280

350

<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:

0.0177

Hom.:

Bravo

AF:

0.0354

Asia WGS

AF:

0.151

AC:

526

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.19

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over