rs66539932

Variant names:

• chr7-128410202-C-T
• rs66539932
• NM_000883.4:c.-301G>A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_000883.4(IMPDH1):​c.-301G>A variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000774 in 297,084 control chromosomes in the GnomAD database, including 1 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 0.000092 (1 hom., cov: 33)
  • Exomes 𝑓: 0.000062 (0 hom.)
• Consequence: IMPDH1 NM_000883.4 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.984

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=-0.77).
• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.0000919 (14/152348) while in subpopulation EAS AF= 0.00155 (8/5178). AF 95% confidence interval is 0.000768. There are 1 homozygotes in gnomad4. There are 8 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 14 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IMPDH1	NM_000883.4	c.-301G>A		upstream_gene_variant		ENST00000338791.11	NP_000874.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IMPDH1	ENST00000338791.11	c.-301G>A		upstream_gene_variant		2	NM_000883.4	ENSP00000345096.6

Frequencies

GnomAD3 genomes AF: 0.0000920 AC: 14 AN: 152230 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.0000482

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00154

Gnomad SAS AF: 0.000827

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000622 AC: 9 AN: 144736 Hom.: 0 Cov.: 0 AF XY: 0.0000823 AC XY: 6 AN XY: 72936

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000386

Gnomad4 SAS exome AF: 0.00103

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.000200

GnomAD4 genome AF: 0.0000919 AC: 14 AN: 152348 Hom.: 1 Cov.: 33 AF XY: 0.000107 AC XY: 8 AN XY: 74508

Gnomad4 AFR AF: 0.0000481

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00154

Gnomad4 SAS AF: 0.000827

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.000110

Asia WGS AF: 0.00144 AC: 5 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	4.9
DANN	Benign	0.68

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs66539932; hg19: chr7-128050256;