dbSNP rs1803822: IMPDH1:c.*634C>T (chr7-128392373-G-A) – ACMG Classification: Benign (-18 pts)

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBS1BS2

The NM_000883.4(IMPDH1):c.*634C>T variant causes a 3 prime UTR change. The variant allele was found at a frequency of 0.0177 in 154,144 control chromosomes in the GnomAD database, including 39 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.018 ( 39 hom., cov: 33)

Exomes 𝑓: 0.013 ( 0 hom. )

Consequence

IMPDH1
NM_000883.4 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 5.03

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:

LOC107986845 (HGNC:):

LOC107986845 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.34).

BP6

Variant 7-128392373-G-A is Benign according to our data. Variant chr7-128392373-G-A is described in ClinVar as [Benign]. Clinvar id is 358858.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0178 (2707/152362) while in subpopulation SAS AF= 0.055 (266/4834). AF 95% confidence interval is 0.0496. There are 39 homozygotes in gnomad4. There are 1329 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 2707 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IMPDH1	NM_000883.4 link	c.*634C>T		3_prime_UTR_variant	Exon 17 of 17	ENST00000338791.11	NP_000874.2	P20839-6B3KRZ3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IMPDH1	ENST00000338791 link	c.*634C>T		3_prime_UTR_variant	Exon 17 of 17	2	NM_000883.4	ENSP00000345096.6		P20839-6

Frequencies

GnomAD3 genomes

AF:

0.0178

AC:

2709

AN:

152244

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00615

Gnomad AMI

AF:

0.00658

Gnomad AMR

AF:

0.0195

Gnomad ASJ

AF:

0.0193

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.0554

Gnomad FIN

AF:

0.00668

Gnomad MID

AF:

0.0348

Gnomad NFE

AF:

0.0248

Gnomad OTH

AF:

0.0211

GnomAD4 exome

AF:

0.0135

AC:

AN:

1782

Hom.:

Cov.:

AF XY:

0.0144

AC XY:

AN XY:

970

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00538

Gnomad4 ASJ exome

AF:

0.0833

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0581

Gnomad4 FIN exome

AF:

0.00214

Gnomad4 NFE exome

AF:

0.0169

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0178

AC:

2707

AN:

152362

Hom.:

Cov.:

AF XY:

0.0178

AC XY:

1329

AN XY:

74510

show subpopulations

Gnomad4 AFR

AF:

0.00613

Gnomad4 AMR

AF:

0.0195

Gnomad4 ASJ

AF:

0.0193

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.0550

Gnomad4 FIN

AF:

0.00668

Gnomad4 NFE

AF:

0.0248

Gnomad4 OTH

AF:

0.0208

Alfa

AF:

0.0194

Hom.:

Bravo

AF:

0.0170

Asia WGS

AF:

0.0280

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Leber congenital amaurosis 11

Benign:1

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Retinitis pigmentosa

Benign:1

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.34

CADD

Benign

DANN

Benign

0.93

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.3

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