dbSNP rs2288552: IMPDH1:c.147-52G>T (chr7-128409536-C-A) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000883.4(IMPDH1):c.147-52G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0395 in 1,602,978 control chromosomes in the GnomAD database, including 2,472 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.049 ( 339 hom., cov: 33)

Exomes 𝑓: 0.039 ( 2133 hom. )

Consequence

IMPDH1
NM_000883.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -3.90

Publications

2 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: Labcorp Genetics (formerly Invitae), Ambry Genetics, 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

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.71).

BP6

Variant 7-128409536-C-A is Benign according to our data. Variant chr7-128409536-C-A is described in ClinVar as Benign. ClinVar VariationId is 1251807.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.201 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.147-52G>T	intron	N/A	NP_000874.2
IMPDH1	NM_001102605.2		c.147-170G>T	intron	N/A	NP_001096075.1	P20839-5
IMPDH1	NM_001142576.2		c.147-52G>T	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.147-52G>T	intron	N/A	ENSP00000345096.6	P20839-6
IMPDH1	ENST00000348127.11	TSL:1	c.146+220G>T	intron	N/A	ENSP00000265385.8	P20839-3
IMPDH1	ENST00000955327.1		c.146+220G>T	intron	N/A	ENSP00000625386.1

Frequencies

GnomAD3 genomes

AF:

0.0490

AC:

7457

AN:

152206

Hom.:

339

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0698

Gnomad AMI

AF:

0.00329

Gnomad AMR

AF:

0.0359

Gnomad ASJ

AF:

0.0637

Gnomad EAS

AF:

0.212

Gnomad SAS

AF:

0.134

Gnomad FIN

AF:

0.00763

Gnomad MID

AF:

0.0665

Gnomad NFE

AF:

0.0269

Gnomad OTH

AF:

0.0516

GnomAD2 exomes

AF:

0.0569

AC:

14295

AN:

251308

AF XY:

0.0592

show subpopulations

Gnomad AFR exome

AF:

0.0716

Gnomad AMR exome

AF:

0.0293

Gnomad ASJ exome

AF:

0.0593

Gnomad EAS exome

AF:

0.218

Gnomad FIN exome

AF:

0.00675

Gnomad NFE exome

AF:

0.0266

Gnomad OTH exome

AF:

0.0473

GnomAD4 exome

AF:

0.0386

AC:

55924

AN:

1450654

Hom.:

2133

Cov.:

AF XY:

0.0410

AC XY:

29592

AN XY:

722370

show subpopulations

African (AFR)

AF:

0.0712

AC:

2364

AN:

33212

American (AMR)

AF:

0.0305

AC:

1365

AN:

44708

Ashkenazi Jewish (ASJ)

AF:

0.0610

AC:

1591

AN:

26068

East Asian (EAS)

AF:

0.180

AC:

7142

AN:

39652

South Asian (SAS)

AF:

0.126

AC:

10873

AN:

85996

European-Finnish (FIN)

AF:

0.00785

AC:

419

AN:

53396

Middle Eastern (MID)

AF:

0.0638

AC:

363

AN:

5688

European-Non Finnish (NFE)

AF:

0.0261

AC:

28719

AN:

1101944

Other (OTH)

AF:

0.0515

AC:

3088

AN:

59990

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

3045

6091

9136

12182

15227

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1292

2584

3876

5168

6460

<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:

0.0489

AC:

7455

AN:

152324

Hom.:

339

Cov.:

AF XY:

0.0504

AC XY:

3752

AN XY:

74488

show subpopulations

African (AFR)

AF:

0.0697

AC:

2899

AN:

41572

American (AMR)

AF:

0.0359

AC:

549

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.0637

AC:

221

AN:

3472

East Asian (EAS)

AF:

0.212

AC:

1097

AN:

5180

South Asian (SAS)

AF:

0.133

AC:

642

AN:

4826

European-Finnish (FIN)

AF:

0.00763

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.0680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0270

AC:

1834

AN:

68028

Other (OTH)

AF:

0.0516

AC:

109

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

349

699

1048

1398

1747

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

184

276

368

460

<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:

0.0311

Hom.:

191

Bravo

AF:

0.0516

Asia WGS

AF:

0.157

AC:

547

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.71

CADD

Benign

0.026

(source)

DANN

Benign

0.92

PhyloP100

-3.9

PromoterAI

-0.00060

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over