chr7-128400698-C-T

Position:

• chr7-128400698-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.579+119G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.451 in 1,180,866 control chromosomes in the GnomAD database, including 121,500 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 0.46 (16500 hom., cov: 33)
  • Exomes 𝑓: 0.45 (105000 hom.)
• Consequence: IMPDH1 NM_000883.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00600

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).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.484 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IMPDH1	NM_000883.4	c.579+119G>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.579+119G>A		intron_variant		2	NM_000883.4	ENSP00000345096

Frequencies

GnomAD3 genomes AF: 0.465 AC: 70638 AN: 151954 Hom.: 16498 Cov.: 33

Gnomad AFR AF: 0.490

Gnomad AMI AF: 0.444

Gnomad AMR AF: 0.449

Gnomad ASJ AF: 0.506

Gnomad EAS AF: 0.409

Gnomad SAS AF: 0.330

Gnomad FIN AF: 0.509

Gnomad MID AF: 0.364

Gnomad NFE AF: 0.459

Gnomad OTH AF: 0.473

GnomAD4 exome AF: 0.448 AC: 461360 AN: 1028794 Hom.: 105000 Cov.: 14 AF XY: 0.444 AC XY: 235718 AN XY: 530700

Gnomad4 AFR exome AF: 0.494

Gnomad4 AMR exome AF: 0.466

Gnomad4 ASJ exome AF: 0.509

Gnomad4 EAS exome AF: 0.393

Gnomad4 SAS exome AF: 0.325

Gnomad4 FIN exome AF: 0.506

Gnomad4 NFE exome AF: 0.456

Gnomad4 OTH exome AF: 0.452

GnomAD4 genome AF: 0.465 AC: 70675 AN: 152072 Hom.: 16500 Cov.: 33 AF XY: 0.463 AC XY: 34410 AN XY: 74342

Gnomad4 AFR AF: 0.489

Gnomad4 AMR AF: 0.449

Gnomad4 ASJ AF: 0.506

Gnomad4 EAS AF: 0.409

Gnomad4 SAS AF: 0.329

Gnomad4 FIN AF: 0.509

Gnomad4 NFE AF: 0.459

Gnomad4 OTH AF: 0.474

Alfa AF: 0.464 Hom.: 9136

Bravo AF: 0.468

Asia WGS AF: 0.373 AC: 1298 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	13
DANN	Benign	0.81

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2278293; hg19: chr7-128040752; COSMIC: COSV58316192; COSMIC: COSV58316192;