dbSNP rs2288553: IMPDH1:c.146+109A>T (chr7-128409647-T-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000883.4(IMPDH1):c.146+109A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0692 in 1,504,898 control chromosomes in the GnomAD database, including 6,384 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.068 ( 738 hom., cov: 33)

Exomes 𝑓: 0.069 ( 5646 hom. )

Consequence

IMPDH1
NM_000883.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.152

Publications

6 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.73).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.225 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IMPDH1	NM_000883.4 link	c.146+109A>T		intron_variant	Intron 1 of 16	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.146+109A>T		intron_variant	Intron 1 of 16	2	NM_000883.4	ENSP00000345096.6		P20839-6

Frequencies

GnomAD3 genomes

AF:

0.0678

AC:

10294

AN:

151916

Hom.:

736

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0155

Gnomad AMI

AF:

0.0165

Gnomad AMR

AF:

0.204

Gnomad ASJ

AF:

0.0393

Gnomad EAS

AF:

0.235

Gnomad SAS

AF:

0.0888

Gnomad FIN

AF:

0.0712

Gnomad MID

AF:

0.0353

Gnomad NFE

AF:

0.0572

Gnomad OTH

AF:

0.0493

GnomAD4 exome

AF:

0.0694

AC:

93838

AN:

1352866

Hom.:

5646

Cov.:

AF XY:

0.0689

AC XY:

46349

AN XY:

672652

show subpopulations

African (AFR)

AF:

0.0113

AC:

352

AN:

31220

American (AMR)

AF:

0.287

AC:

10658

AN:

37126

Ashkenazi Jewish (ASJ)

AF:

0.0373

AC:

930

AN:

24940

East Asian (EAS)

AF:

0.284

AC:

10513

AN:

37062

South Asian (SAS)

AF:

0.0890

AC:

7194

AN:

80856

European-Finnish (FIN)

AF:

0.0836

AC:

3837

AN:

45902

Middle Eastern (MID)

AF:

0.0340

AC:

136

AN:

4004

European-Non Finnish (NFE)

AF:

0.0546

AC:

56487

AN:

1035280

Other (OTH)

AF:

0.0661

AC:

3731

AN:

56476

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

4667

9333

14000

18666

23333

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2248

4496

6744

8992

11240

<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:

0.0677

AC:

10295

AN:

152032

Hom.:

738

Cov.:

AF XY:

0.0728

AC XY:

5412

AN XY:

74342

show subpopulations

African (AFR)

AF:

0.0155

AC:

641

AN:

41482

American (AMR)

AF:

0.204

AC:

3116

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.0393

AC:

136

AN:

3464

East Asian (EAS)

AF:

0.236

AC:

1215

AN:

5158

South Asian (SAS)

AF:

0.0877

AC:

422

AN:

4814

European-Finnish (FIN)

AF:

0.0712

AC:

755

AN:

10610

Middle Eastern (MID)

AF:

0.0414

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.0572

AC:

3882

AN:

67904

Other (OTH)

AF:

0.0479

AC:

101

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

469

938

1407

1876

2345

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

112

224

336

448

560

<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:

0.0561

Hom.:

Bravo

AF:

0.0746

Asia WGS

AF:

0.170

AC:

590

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.73

CADD

Benign

7.0

(source)

DANN

Benign

0.80

PhyloP100

-0.15

PromoterAI

0.084

Neutral

(source)

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over