Variant rs28580600 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000883.4(IMPDH1):c.1405+33C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.122 in 1,613,794 control chromosomes in the GnomAD database, including 13,051 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.13 ( 1236 hom., cov: 33)

Exomes 𝑓: 0.12 ( 11815 hom. )

Consequence

IMPDH1
NM_000883.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.73

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.93).

BP6

Variant 7-128395098-G-A is Benign according to our data. Variant chr7-128395098-G-A is described in ClinVar as [Benign]. Clinvar id is 1291045.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.141 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IMPDH1	NM_000883.4 linkuse as main transcript	c.1405+33C>T		intron_variant		ENST00000338791.11	NP_000874.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IMPDH1	ENST00000338791.11 linkuse as main transcript	c.1405+33C>T		intron_variant		2	NM_000883.4	ENSP00000345096		P20839-6

Frequencies

GnomAD3 genomes

AF:

0.125

AC:

19018

AN:

152098

Hom.:

1235

Cov.:

show subpopulations

Gnomad AFR

AF:

0.144

Gnomad AMI

AF:

0.163

Gnomad AMR

AF:

0.0980

Gnomad ASJ

AF:

0.133

Gnomad EAS

AF:

0.000578

Gnomad SAS

AF:

0.0314

Gnomad FIN

AF:

0.120

Gnomad MID

AF:

0.165

Gnomad NFE

AF:

0.135

Gnomad OTH

AF:

0.150

GnomAD3 exomes

AF:

0.104

AC:

26137

AN:

251140

Hom.:

1716

AF XY:

0.103

AC XY:

14014

AN XY:

135810

show subpopulations

Gnomad AFR exome

AF:

0.144

Gnomad AMR exome

AF:

0.0739

Gnomad ASJ exome

AF:

0.135

Gnomad EAS exome

AF:

0.000435

Gnomad SAS exome

AF:

0.0303

Gnomad FIN exome

AF:

0.118

Gnomad NFE exome

AF:

0.138

Gnomad OTH exome

AF:

0.129

GnomAD4 exome

AF:

0.122

AC:

178238

AN:

1461578

Hom.:

11815

Cov.:

AF XY:

0.120

AC XY:

86983

AN XY:

727102

show subpopulations

Gnomad4 AFR exome

AF:

0.148

Gnomad4 AMR exome

AF:

0.0801

Gnomad4 ASJ exome

AF:

0.137

Gnomad4 EAS exome

AF:

0.000252

Gnomad4 SAS exome

AF:

0.0310

Gnomad4 FIN exome

AF:

0.118

Gnomad4 NFE exome

AF:

0.134

Gnomad4 OTH exome

AF:

0.122

GnomAD4 genome

AF:

0.125

AC:

19030

AN:

152216

Hom.:

1236

Cov.:

AF XY:

0.121

AC XY:

8991

AN XY:

74428

show subpopulations

Gnomad4 AFR

AF:

0.144

Gnomad4 AMR

AF:

0.0977

Gnomad4 ASJ

AF:

0.133

Gnomad4 EAS

AF:

0.000579

Gnomad4 SAS

AF:

0.0317

Gnomad4 FIN

AF:

0.120

Gnomad4 NFE

AF:

0.135

Gnomad4 OTH

AF:

0.148

Alfa

AF:

0.0853

Hom.:

138

Bravo

AF:

0.128

Asia WGS

AF:

0.0270

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

0.013

DANN

Benign

0.35

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over