Variant 7-128409536-C-A 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.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

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:

IMPDH1 (HGNC:):

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=-0.71).

BP6

Variant 7-128409536-C-A is Benign according to our data. Variant chr7-128409536-C-A is described in ClinVar as [Benign]. Clinvar id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IMPDH1	NM_000883.4 linkuse as main transcript	c.147-52G>T		intron_variant		ENST00000338791.11	NP_000874.2	P20839-6B3KRZ3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IMPDH1	ENST00000338791.11 linkuse as main transcript	c.147-52G>T		intron_variant		2	NM_000883.4	ENSP00000345096.6		P20839-6

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

GnomAD3 exomes

AF:

0.0569

AC:

14295

AN:

251308

Hom.:

878

AF XY:

0.0592

AC XY:

8040

AN XY:

135880

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 SAS exome

AF:

0.132

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

Gnomad4 AFR exome

AF:

0.0712

Gnomad4 AMR exome

AF:

0.0305

Gnomad4 ASJ exome

AF:

0.0610

Gnomad4 EAS exome

AF:

0.180

Gnomad4 SAS exome

AF:

0.126

Gnomad4 FIN exome

AF:

0.00785

Gnomad4 NFE exome

AF:

0.0261

Gnomad4 OTH exome

AF:

0.0515

GnomAD4 genome

AF:

0.0489

AC:

7455

AN:

152324

Hom.:

339

Cov.:

AF XY:

0.0504

AC XY:

3752

AN XY:

74488

show subpopulations

Gnomad4 AFR

AF:

0.0697

Gnomad4 AMR

AF:

0.0359

Gnomad4 ASJ

AF:

0.0637

Gnomad4 EAS

AF:

0.212

Gnomad4 SAS

AF:

0.133

Gnomad4 FIN

AF:

0.00763

Gnomad4 NFE

AF:

0.0270

Gnomad4 OTH

AF:

0.0516

Alfa

AF:

0.0223

Hom.:

Bravo

AF:

0.0516

Asia WGS

AF:

0.157

AC:

547

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

-0.71

CADD

Benign

0.026

DANN

Benign

0.92

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

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