rs72624952

Positions:

• chr7-128400925-G-T

Variant summary

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

The NM_000883.4(IMPDH1):​c.505-34C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0175 in 1,604,996 control chromosomes in the GnomAD database, including 312 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 0.012 (21 hom., cov: 33)
  • Exomes 𝑓: 0.018 (291 hom.)
• Consequence: IMPDH1 NM_000883.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.03

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=-0.8).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0124 (1882/152220) while in subpopulation NFE AF= 0.0211 (1436/68022). AF 95% confidence interval is 0.0202. There are 21 homozygotes in gnomad4. There are 868 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 1882 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IMPDH1	NM_000883.4	c.505-34C>A		intron_variant		ENST00000338791.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IMPDH1	ENST00000338791.11	c.505-34C>A		intron_variant		2	NM_000883.4

Frequencies

GnomAD3 genomes AF: 0.0124 AC: 1883 AN: 152102 Hom.: 21 Cov.: 33

Gnomad AFR AF: 0.00341

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.00498

Gnomad ASJ AF: 0.00374

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000828

Gnomad FIN AF: 0.0190

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0211

Gnomad OTH AF: 0.00526

GnomAD3 exomes AF: 0.0128 AC: 3227 AN: 251296 Hom.: 25 AF XY: 0.0129 AC XY: 1754 AN XY: 135858

Gnomad AFR exome AF: 0.00425

Gnomad AMR exome AF: 0.00483

Gnomad ASJ exome AF: 0.00367

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00118

Gnomad FIN exome AF: 0.0209

Gnomad NFE exome AF: 0.0211

Gnomad OTH exome AF: 0.0112

GnomAD4 exome AF: 0.0180 AC: 26149 AN: 1452776 Hom.: 291 Cov.: 30 AF XY: 0.0175 AC XY: 12690 AN XY: 723250

Gnomad4 AFR exome AF: 0.00285

Gnomad4 AMR exome AF: 0.00526

Gnomad4 ASJ exome AF: 0.00468

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00130

Gnomad4 FIN exome AF: 0.0211

Gnomad4 NFE exome AF: 0.0215

Gnomad4 OTH exome AF: 0.0120

GnomAD4 genome AF: 0.0124 AC: 1882 AN: 152220 Hom.: 21 Cov.: 33 AF XY: 0.0117 AC XY: 868 AN XY: 74412

Gnomad4 AFR AF: 0.00340

Gnomad4 AMR AF: 0.00490

Gnomad4 ASJ AF: 0.00374

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000829

Gnomad4 FIN AF: 0.0190

Gnomad4 NFE AF: 0.0211

Gnomad4 OTH AF: 0.00521

Alfa AF: 0.0139 Hom.: 3

Bravo AF: 0.0107

Asia WGS AF: 0.00231 AC: 8 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	2.2
DANN	Benign	0.80
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs72624952; hg19: chr7-128040979; COSMIC: COSV58317411; COSMIC: COSV58317411;