rs28580600

chr7-128395098-G-Achr7-128395098-G-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.73

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]

ACMG classification

Verdict is Benign. Variant got -14 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_single_submitter, 1 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	UniProt
IMPDH1	NM_000883.4	c.1405+33C>T		intron_variant		ENST00000338791.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IMPDH1	ENST00000338791.11	c.1405+33C>T		intron_variant		2	NM_000883.4

Frequencies

GnomAD3 genomes AF: 0.125 AC: 19018 AN: 152098 Hom.: 1235 Cov.: 33

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

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.: 35 AF XY: 0.120 AC XY: 86983 AN XY: 727102

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.: 33 AF XY: 0.121 AC XY: 8991 AN XY: 74428

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: 94 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

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

Other links and lift over

dbSNP: rs28580600; hg19: chr7-128035152;