rs2288553

Positions:

• chr7-128409647-T-A
• chr7-128409647-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000883.4(IMPDH1):​c.146+109A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0692 in 1,504,898 control chromosomes in the GnomAD database, including 6,384 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.068 (738 hom., cov: 33)
  • Exomes 𝑓: 0.069 (5646 hom.)
• Consequence: IMPDH1 NM_000883.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.152

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.225 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IMPDH1	NM_000883.4	c.146+109A>T		intron_variant		ENST00000338791.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IMPDH1	ENST00000338791.11	c.146+109A>T		intron_variant		2	NM_000883.4

Frequencies

GnomAD3 genomes AF: 0.0678 AC: 10294 AN: 151916 Hom.: 736 Cov.: 33

Gnomad AFR AF: 0.0155

Gnomad AMI AF: 0.0165

Gnomad AMR AF: 0.204

Gnomad ASJ AF: 0.0393

Gnomad EAS AF: 0.235

Gnomad SAS AF: 0.0888

Gnomad FIN AF: 0.0712

Gnomad MID AF: 0.0353

Gnomad NFE AF: 0.0572

Gnomad OTH AF: 0.0493

GnomAD4 exome AF: 0.0694 AC: 93838 AN: 1352866 Hom.: 5646 Cov.: 23 AF XY: 0.0689 AC XY: 46349 AN XY: 672652

Gnomad4 AFR exome AF: 0.0113

Gnomad4 AMR exome AF: 0.287

Gnomad4 ASJ exome AF: 0.0373

Gnomad4 EAS exome AF: 0.284

Gnomad4 SAS exome AF: 0.0890

Gnomad4 FIN exome AF: 0.0836

Gnomad4 NFE exome AF: 0.0546

Gnomad4 OTH exome AF: 0.0661

GnomAD4 genome AF: 0.0677 AC: 10295 AN: 152032 Hom.: 738 Cov.: 33 AF XY: 0.0728 AC XY: 5412 AN XY: 74342

Gnomad4 AFR AF: 0.0155

Gnomad4 AMR AF: 0.204

Gnomad4 ASJ AF: 0.0393

Gnomad4 EAS AF: 0.236

Gnomad4 SAS AF: 0.0877

Gnomad4 FIN AF: 0.0712

Gnomad4 NFE AF: 0.0572

Gnomad4 OTH AF: 0.0479

Alfa AF: 0.0561 Hom.: 47

Bravo AF: 0.0746

Asia WGS AF: 0.170 AC: 590 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	7.0
DANN	Benign	0.80

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2288553; hg19: chr7-128049701; COSMIC: COSV58316515; COSMIC: COSV58316515;