rs4731447

Positions:

• chr7-128394713-A-C

Variant summary

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

The NM_000883.4(IMPDH1):​c.1551-114T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0719 in 1,444,702 control chromosomes in the GnomAD database, including 6,695 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 0.074 (774 hom., cov: 32)
  • Exomes 𝑓: 0.072 (5921 hom.)
• Consequence: IMPDH1 NM_000883.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.02

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=-0.93).
• 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.1551-114T>G		intron_variant		ENST00000338791.11	NP_000874.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IMPDH1	ENST00000338791.11	c.1551-114T>G		intron_variant		2	NM_000883.4	ENSP00000345096

Frequencies

GnomAD3 genomes AF: 0.0736 AC: 11197 AN: 152052 Hom.: 769 Cov.: 32

Gnomad AFR AF: 0.0349

Gnomad AMI AF: 0.0186

Gnomad AMR AF: 0.207

Gnomad ASJ AF: 0.0395

Gnomad EAS AF: 0.235

Gnomad SAS AF: 0.0894

Gnomad FIN AF: 0.0734

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0572

Gnomad OTH AF: 0.0533

GnomAD4 exome AF: 0.0717 AC: 92686 AN: 1292532 Hom.: 5921 Cov.: 19 AF XY: 0.0708 AC XY: 45974 AN XY: 649280

Gnomad4 AFR exome AF: 0.0328

Gnomad4 AMR exome AF: 0.296

Gnomad4 ASJ exome AF: 0.0373

Gnomad4 EAS exome AF: 0.288

Gnomad4 SAS exome AF: 0.0898

Gnomad4 FIN exome AF: 0.0869

Gnomad4 NFE exome AF: 0.0543

Gnomad4 OTH exome AF: 0.0674

GnomAD4 genome AF: 0.0737 AC: 11217 AN: 152170 Hom.: 774 Cov.: 32 AF XY: 0.0787 AC XY: 5855 AN XY: 74380

Gnomad4 AFR AF: 0.0353

Gnomad4 AMR AF: 0.207

Gnomad4 ASJ AF: 0.0395

Gnomad4 EAS AF: 0.236

Gnomad4 SAS AF: 0.0883

Gnomad4 FIN AF: 0.0734

Gnomad4 NFE AF: 0.0572

Gnomad4 OTH AF: 0.0518

Alfa AF: 0.0604 Hom.: 61

Bravo AF: 0.0813

Asia WGS AF: 0.176 AC: 610 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.054
DANN	Benign	0.38

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: rs4731447; hg19: chr7-128034767;