rs2288551

chr7-128409519-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000883.4(IMPDH1):c.147-35G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0395 in 1,611,944 control chromosomes in the GnomAD database, including 2,478 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.049 (338 hom., cov: 33)
  • Exomes 𝑓: 0.039 (2140 hom.)
• Consequence: IMPDH1 NM_000883.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0750

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BP6: Variant 7-128409519-C-T is Benign according to our data. Variant chr7-128409519-C-T is described in ClinVar as [Benign]. Clinvar id is 1181857.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.202 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IMPDH1	NM_000883.4	c.147-35G>A		intron_variant		ENST00000338791.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IMPDH1	ENST00000338791.11	c.147-35G>A		intron_variant		2	NM_000883.4

Frequencies

GnomAD3 genomes AF: 0.0490 AC: 7461 AN: 152184 Hom.: 338 Cov.: 33

Gnomad AFR AF: 0.0699

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.0358

Gnomad ASJ AF: 0.0637

Gnomad EAS AF: 0.212

Gnomad SAS AF: 0.134

Gnomad FIN AF: 0.00762

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0270

Gnomad OTH AF: 0.0517

GnomAD3 exomes AF: 0.0569 AC: 14294 AN: 251382 Hom.: 878 AF XY: 0.0591 AC XY: 8038 AN XY: 135914

Gnomad AFR exome AF: 0.0714

Gnomad AMR exome AF: 0.0293

Gnomad ASJ exome AF: 0.0593

Gnomad EAS exome AF: 0.218

Gnomad SAS exome AF: 0.132

Gnomad FIN exome AF: 0.00674

Gnomad NFE exome AF: 0.0265

Gnomad OTH exome AF: 0.0474

GnomAD4 exome AF: 0.0385 AC: 56269 AN: 1459642 Hom.: 2140 Cov.: 30 AF XY: 0.0410 AC XY: 29750 AN XY: 726246

Gnomad4 AFR exome AF: 0.0714

Gnomad4 AMR exome AF: 0.0306

Gnomad4 ASJ exome AF: 0.0610

Gnomad4 EAS exome AF: 0.180

Gnomad4 SAS exome AF: 0.126

Gnomad4 FIN exome AF: 0.00785

Gnomad4 NFE exome AF: 0.0261

Gnomad4 OTH exome AF: 0.0516

GnomAD4 genome AF: 0.0490 AC: 7459 AN: 152302 Hom.: 338 Cov.: 33 AF XY: 0.0504 AC XY: 3755 AN XY: 74468

Gnomad4 AFR AF: 0.0698

Gnomad4 AMR AF: 0.0358

Gnomad4 ASJ AF: 0.0637

Gnomad4 EAS AF: 0.212

Gnomad4 SAS AF: 0.133

Gnomad4 FIN AF: 0.00762

Gnomad4 NFE AF: 0.0270

Gnomad4 OTH AF: 0.0516

Alfa AF: 0.0389 Hom.: 34

Bravo AF: 0.0516

Asia WGS AF: 0.157 AC: 547 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 03, 2015

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
Cadd	Benign	13
Dann	Benign	0.93
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2288551; hg19: chr7-128049573; COSMIC: COSV58315368; COSMIC: COSV58315368;