chr7-128394413-C-T

Position:

• chr7-128394413-C-T

Variant summary

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

The NM_000883.4(IMPDH1):​c.1694+43G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0705 in 1,613,460 control chromosomes in the GnomAD database, including 7,199 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 (740 hom., cov: 32)
  • Exomes 𝑓: 0.071 (6459 hom.)
• Consequence: IMPDH1 NM_000883.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0490

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=-0.75).
• 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	Protein	UniProt
IMPDH1	NM_000883.4	c.1694+43G>A		intron_variant		ENST00000338791.11	NP_000874.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IMPDH1	ENST00000338791.11	c.1694+43G>A		intron_variant		2	NM_000883.4	ENSP00000345096

Frequencies

GnomAD3 genomes AF: 0.0678 AC: 10307 AN: 151922 Hom.: 735 Cov.: 32

Gnomad AFR AF: 0.0158

Gnomad AMI AF: 0.0186

Gnomad AMR AF: 0.204

Gnomad ASJ AF: 0.0389

Gnomad EAS AF: 0.235

Gnomad SAS AF: 0.0885

Gnomad FIN AF: 0.0732

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0570

Gnomad OTH AF: 0.0494

GnomAD3 exomes AF: 0.109 AC: 27331 AN: 251242 Hom.: 2828 AF XY: 0.0997 AC XY: 13546 AN XY: 135828

Gnomad AFR exome AF: 0.0165

Gnomad AMR exome AF: 0.311

Gnomad ASJ exome AF: 0.0378

Gnomad EAS exome AF: 0.224

Gnomad SAS exome AF: 0.0912

Gnomad FIN exome AF: 0.0836

Gnomad NFE exome AF: 0.0589

Gnomad OTH exome AF: 0.0860

GnomAD4 exome AF: 0.0708 AC: 103443 AN: 1461420 Hom.: 6459 Cov.: 34 AF XY: 0.0699 AC XY: 50840 AN XY: 727040

Gnomad4 AFR exome AF: 0.0116

Gnomad4 AMR exome AF: 0.296

Gnomad4 ASJ exome AF: 0.0373

Gnomad4 EAS exome AF: 0.286

Gnomad4 SAS exome AF: 0.0903

Gnomad4 FIN exome AF: 0.0856

Gnomad4 NFE exome AF: 0.0548

Gnomad4 OTH exome AF: 0.0664

GnomAD4 genome AF: 0.0679 AC: 10320 AN: 152040 Hom.: 740 Cov.: 32 AF XY: 0.0730 AC XY: 5421 AN XY: 74288

Gnomad4 AFR AF: 0.0161

Gnomad4 AMR AF: 0.204

Gnomad4 ASJ AF: 0.0389

Gnomad4 EAS AF: 0.236

Gnomad4 SAS AF: 0.0873

Gnomad4 FIN AF: 0.0732

Gnomad4 NFE AF: 0.0570

Gnomad4 OTH AF: 0.0479

Alfa AF: 0.0344 Hom.: 41

Bravo AF: 0.0748

Asia WGS AF: 0.174 AC: 603 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	7.3
DANN	Benign	0.71

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: rs72624969; hg19: chr7-128034467; COSMIC: COSV58315397; COSMIC: COSV58315397;