Genetic Variant NM_000883.4:c.580-106G>A (chr7-128400645-C-T) – 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.580-106G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.362 in 1,265,432 control chromosomes in the GnomAD database, including 84,562 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 0.38 ( 10997 hom., cov: 33)

Exomes 𝑓: 0.36 ( 73565 hom. )

Consequence

IMPDH1
NM_000883.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.555

Publications

38 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.528 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.580-106G>A	intron	N/A	NP_000874.2
IMPDH1	NM_001102605.2		c.550-106G>A	intron	N/A	NP_001096075.1	P20839-5
IMPDH1	NM_001142576.2		c.481-106G>A	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.580-106G>A	intron	N/A	ENSP00000345096.6	P20839-6
IMPDH1	ENST00000348127.11	TSL:1	c.472-106G>A	intron	N/A	ENSP00000265385.8	P20839-3
IMPDH1	ENST00000955327.1		c.472-106G>A	intron	N/A	ENSP00000625386.1

Frequencies

GnomAD3 genomes

AF:

0.378

AC:

57376

AN:

151962

Hom.:

10997

Cov.:

show subpopulations

Gnomad AFR

AF:

0.406

Gnomad AMI

AF:

0.267

Gnomad AMR

AF:

0.379

Gnomad ASJ

AF:

0.432

Gnomad EAS

AF:

0.545

Gnomad SAS

AF:

0.430

Gnomad FIN

AF:

0.374

Gnomad MID

AF:

0.269

Gnomad NFE

AF:

0.343

Gnomad OTH

AF:

0.365

GnomAD4 exome

AF:

0.360

AC:

400663

AN:

1113352

Hom.:

73565

Cov.:

AF XY:

0.362

AC XY:

205092

AN XY:

566678

show subpopulations

African (AFR)

AF:

0.402

AC:

10672

AN:

26542

American (AMR)

AF:

0.407

AC:

16080

AN:

39536

Ashkenazi Jewish (ASJ)

AF:

0.428

AC:

10134

AN:

23672

East Asian (EAS)

AF:

0.500

AC:

18556

AN:

37118

South Asian (SAS)

AF:

0.416

AC:

32329

AN:

77708

European-Finnish (FIN)

AF:

0.379

AC:

19699

AN:

51918

Middle Eastern (MID)

AF:

0.330

AC:

1375

AN:

4162

European-Non Finnish (NFE)

AF:

0.341

AC:

273907

AN:

804054

Other (OTH)

AF:

0.368

AC:

17911

AN:

48642

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

14327

28654

42982

57309

71636

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7764

15528

23292

31056

38820

<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:

0.378

AC:

57415

AN:

152080

Hom.:

10997

Cov.:

AF XY:

0.381

AC XY:

28312

AN XY:

74330

show subpopulations

African (AFR)

AF:

0.406

AC:

16840

AN:

41498

American (AMR)

AF:

0.380

AC:

5807

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.432

AC:

1499

AN:

3468

East Asian (EAS)

AF:

0.545

AC:

2813

AN:

5164

South Asian (SAS)

AF:

0.428

AC:

2063

AN:

4816

European-Finnish (FIN)

AF:

0.374

AC:

3960

AN:

10584

Middle Eastern (MID)

AF:

0.259

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.343

AC:

23338

AN:

67952

Other (OTH)

AF:

0.368

AC:

776

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

1855

3709

5564

7418

9273

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

554

1108

1662

2216

2770

<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:

0.358

Hom.:

28537

Bravo

AF:

0.380

Asia WGS

AF:

0.474

AC:

1651

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

1.3

(source)

DANN

Benign

0.59

PhyloP100

-0.56

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

Details are displayed if max score is > 0.2

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