Genetic Variant IMPDH1:c.-184C>T (chr7-128410085-G-A) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_000883.4(IMPDH1):c.-184C>T variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000294 in 441,930 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000038 ( 0 hom. )

Consequence

IMPDH1
NM_000883.4 upstream_gene

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -5.72

Publications

0 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:

ENSG00000302195 (HGNC:):

ENSG00000302195 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BS2

High AC in GnomAdExome4 at 11 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IMPDH1	NM_000883.4 link	c.-184C>T		upstream_gene_variant		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.-184C>T		upstream_gene_variant		2	NM_000883.4	ENSP00000345096.6		P20839-6

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152212

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000380

AC:

AN:

289600

Hom.:

Cov.:

AF XY:

0.0000338

AC XY:

AN XY:

147724

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

7064

American (AMR)

AF:

0.00

AC:

AN:

7008

Ashkenazi Jewish (ASJ)

AF:

0.000107

AC:

AN:

9384

East Asian (EAS)

AF:

0.000459

AC:

AN:

21766

South Asian (SAS)

AF:

0.00

AC:

AN:

9646

European-Finnish (FIN)

AF:

0.00

AC:

AN:

22574

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1388

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

192688

Other (OTH)

AF:

0.00

AC:

AN:

18082

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.0000131

AC:

AN:

152330

Hom.:

Cov.:

AF XY:

0.0000268

AC XY:

AN XY:

74500

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41586

American (AMR)

AF:

0.00

AC:

AN:

15312

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.000386

AC:

AN:

5180

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68010

Other (OTH)

AF:

0.00

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.49

(source)

DANN

Benign

0.86

PhyloP100

-5.7

PromoterAI

-0.038

Neutral

(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