7-128395076-ACC-AC

Position:

• chr7-128395076-ACC-AC

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_000883.4(IMPDH1):​c.1406-44delG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0368 in 1,612,738 control chromosomes in the GnomAD database, including 2,258 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.035 (219 hom., cov: 32)
  • Exomes 𝑓: 0.037 (2039 hom.)
• Consequence: IMPDH1 NM_000883.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.188

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 7-128395076-AC-A is Benign according to our data. Variant chr7-128395076-AC-A is described in ClinVar as [Benign]. Clinvar id is 1259283.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.2 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IMPDH1	NM_000883.4	c.1406-44delG		intron_variant		ENST00000338791.11	NP_000874.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IMPDH1	ENST00000338791.11	c.1406-44delG		intron_variant		2	NM_000883.4	ENSP00000345096.6

Frequencies

GnomAD3 genomes AF: 0.0346 AC: 5240 AN: 151312 Hom.: 219 Cov.: 32

Gnomad AFR AF: 0.0190

Gnomad AMI AF: 0.00330

Gnomad AMR AF: 0.0312

Gnomad ASJ AF: 0.0673

Gnomad EAS AF: 0.210

Gnomad SAS AF: 0.137

Gnomad FIN AF: 0.00771

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0269

Gnomad OTH AF: 0.0434

GnomAD3 exomes AF: 0.0534 AC: 13365 AN: 250410 Hom.: 825 AF XY: 0.0566 AC XY: 7676 AN XY: 135640

Gnomad AFR exome AF: 0.0204

Gnomad AMR exome AF: 0.0272

Gnomad ASJ exome AF: 0.0628

Gnomad EAS exome AF: 0.216

Gnomad SAS exome AF: 0.133

Gnomad FIN exome AF: 0.00678

Gnomad NFE exome AF: 0.0266

Gnomad OTH exome AF: 0.0469

GnomAD4 exome AF: 0.0371 AC: 54171 AN: 1461312 Hom.: 2039 Cov.: 32 AF XY: 0.0398 AC XY: 28909 AN XY: 726978

Gnomad4 AFR exome AF: 0.0188

Gnomad4 AMR exome AF: 0.0285

Gnomad4 ASJ exome AF: 0.0649

Gnomad4 EAS exome AF: 0.176

Gnomad4 SAS exome AF: 0.127

Gnomad4 FIN exome AF: 0.00789

Gnomad4 NFE exome AF: 0.0260

Gnomad4 OTH exome AF: 0.0487

GnomAD4 genome AF: 0.0346 AC: 5233 AN: 151426 Hom.: 219 Cov.: 32 AF XY: 0.0365 AC XY: 2698 AN XY: 73952

Gnomad4 AFR AF: 0.0189

Gnomad4 AMR AF: 0.0312

Gnomad4 ASJ AF: 0.0673

Gnomad4 EAS AF: 0.210

Gnomad4 SAS AF: 0.136

Gnomad4 FIN AF: 0.00771

Gnomad4 NFE AF: 0.0269

Gnomad4 OTH AF: 0.0435

Alfa AF: 0.0177 Hom.: 14

Bravo AF: 0.0354

Asia WGS AF: 0.151 AC: 526 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 03, 2015

- -

Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs72624966; hg19: chr7-128035130;