chr7-128392731-G-A

Position:

• chr7-128392731-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Moderate BP6_Moderate BS1 BS2

The NM_000883.4(IMPDH1):​c.*276C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00464 in 486,814 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0042 (2 hom., cov: 33)
  • Exomes 𝑓: 0.0048 (8 hom.)
• Consequence: IMPDH1 NM_000883.4 3_prime_UTR
• Clinical Significance: Benign/Likely benign criteria provided, single submitter B:2
• Conservation: PhyloP100: 0.767

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=-0.42).
• BP6: Variant 7-128392731-G-A is Benign according to our data. Variant chr7-128392731-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 910679.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00419 (638/152250) while in subpopulation NFE AF= 0.00649 (441/67976). AF 95% confidence interval is 0.00599. There are 2 homozygotes in gnomad4. There are 295 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 638 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IMPDH1	NM_000883.4	c.*276C>T		3_prime_UTR_variant	17/17	ENST00000338791.11	NP_000874.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IMPDH1	ENST00000338791.11	c.*276C>T		3_prime_UTR_variant	17/17	2	NM_000883.4	ENSP00000345096

Frequencies

GnomAD3 genomes AF: 0.00419 AC: 638 AN: 152132 Hom.: 2 Cov.: 33

Gnomad AFR AF: 0.00135

Gnomad AMI AF: 0.0110

Gnomad AMR AF: 0.00262

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00310

Gnomad FIN AF: 0.00640

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00649

Gnomad OTH AF: 0.00383

GnomAD4 exome AF: 0.00484 AC: 1620 AN: 334564 Hom.: 8 Cov.: 0 AF XY: 0.00467 AC XY: 823 AN XY: 176214

Gnomad4 AFR exome AF: 0.000942

Gnomad4 AMR exome AF: 0.00169

Gnomad4 ASJ exome AF: 0.0000973

Gnomad4 EAS exome AF: 0.0000899

Gnomad4 SAS exome AF: 0.00428

Gnomad4 FIN exome AF: 0.00618

Gnomad4 NFE exome AF: 0.00609

Gnomad4 OTH exome AF: 0.00407

GnomAD4 genome AF: 0.00419 AC: 638 AN: 152250 Hom.: 2 Cov.: 33 AF XY: 0.00396 AC XY: 295 AN XY: 74428

Gnomad4 AFR AF: 0.00135

Gnomad4 AMR AF: 0.00261

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00311

Gnomad4 FIN AF: 0.00640

Gnomad4 NFE AF: 0.00649

Gnomad4 OTH AF: 0.00379

Alfa AF: 0.00429 Hom.: 0

Bravo AF: 0.00374

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

Submissions by phenotype

Leber congenital amaurosis 11 Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Apr 27, 2017

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -

Retinitis pigmentosa Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Apr 27, 2017

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.42
CADD	Benign	14
DANN	Benign	0.89

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs72624977; hg19: chr7-128032785;