rs2288552

Variant names:

• chr7-128409536-C-A
• rs2288552
• NM_000883.4:c.147-52G>T

Your query was ambiguous. Multiple possible variants found:

• chr7-128409536-C-A
• chr7-128409536-C-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000883.4(IMPDH1):​c.147-52G>T 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 1,602,978 control chromosomes in the GnomAD database, including 2,472 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.049 (339 hom., cov: 33)
  • Exomes 𝑓: 0.039 (2133 hom.)
• Consequence: IMPDH1 NM_000883.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -3.90
• Publications: 2 publications found

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]

IMPDH1 Gene-Disease associations (from GenCC):

• inherited retinal dystrophy

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• Leber congenital amaurosis 11

  Inheritance: AD Classification: DEFINITIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P
• retinitis pigmentosa 10

  Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
• Leber congenital amaurosis

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• retinitis pigmentosa

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BP6: Variant 7-128409536-C-A is Benign according to our data. Variant chr7-128409536-C-A is described in ClinVar as Benign. ClinVar VariationId is 1251807.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.201 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IMPDH1	NM_000883.4	c.147-52G>T		intron_variant	Intron 1 of 16	ENST00000338791.11	NP_000874.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IMPDH1	ENST00000338791.11	c.147-52G>T		intron_variant	Intron 1 of 16	2	NM_000883.4	ENSP00000345096.6

Frequencies

GnomAD3 genomes AF: 0.0490 AC: 7457 AN: 152206 Hom.: 339 Cov.: 33

Gnomad AFR AF: 0.0698

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.0359

Gnomad ASJ AF: 0.0637

Gnomad EAS AF: 0.212

Gnomad SAS AF: 0.134

Gnomad FIN AF: 0.00763

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0269

Gnomad OTH AF: 0.0516

GnomAD2 exomes AF: 0.0569 AC: 14295 AN: 251308 AF XY: 0.0592

Gnomad AFR exome AF: 0.0716

Gnomad AMR exome AF: 0.0293

Gnomad ASJ exome AF: 0.0593

Gnomad EAS exome AF: 0.218

Gnomad FIN exome AF: 0.00675

Gnomad NFE exome AF: 0.0266

Gnomad OTH exome AF: 0.0473

GnomAD4 exome AF: 0.0386 AC: 55924 AN: 1450654 Hom.: 2133 Cov.: 28 AF XY: 0.0410 AC XY: 29592 AN XY: 722370

African (AFR) AF: 0.0712 AC: 2364 AN: 33212

American (AMR) AF: 0.0305 AC: 1365 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.0610 AC: 1591 AN: 26068

East Asian (EAS) AF: 0.180 AC: 7142 AN: 39652

South Asian (SAS) AF: 0.126 AC: 10873 AN: 85996

European-Finnish (FIN) AF: 0.00785 AC: 419 AN: 53396

Middle Eastern (MID) AF: 0.0638 AC: 363 AN: 5688

European-Non Finnish (NFE) AF: 0.0261 AC: 28719 AN: 1101944

Other (OTH) AF: 0.0515 AC: 3088 AN: 59990

GnomAD4 genome AF: 0.0489 AC: 7455 AN: 152324 Hom.: 339 Cov.: 33 AF XY: 0.0504 AC XY: 3752 AN XY: 74488

African (AFR) AF: 0.0697 AC: 2899 AN: 41572

American (AMR) AF: 0.0359 AC: 549 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0637 AC: 221 AN: 3472

East Asian (EAS) AF: 0.212 AC: 1097 AN: 5180

South Asian (SAS) AF: 0.133 AC: 642 AN: 4826

European-Finnish (FIN) AF: 0.00763 AC: 81 AN: 10622

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.0270 AC: 1834 AN: 68028

Other (OTH) AF: 0.0516 AC: 109 AN: 2114

Alfa AF: 0.0311 Hom.: 191

Bravo AF: 0.0516

Asia WGS AF: 0.157 AC: 547 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

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Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	0.026
DANN	Benign	0.92
PhyloP100		-3.9
PromoterAI		-0.00060	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs2288552; hg19: chr7-128049590; COSMIC: COSV58315382; COSMIC: COSV58315382;