rs10484358

Variant names:

• chr6-16255812-G-T
• rs10484358
• NM_006877.4:c.465+1077G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006877.4(GMPR):​c.465+1077G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0747 in 152,094 control chromosomes in the GnomAD database, including 435 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 0.075 (435 hom., cov: 31)
• Consequence: GMPR NM_006877.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.866
• Publications: 9 publications found

Genes affected

GMPR (HGNC:4376): (guanosine monophosphate reductase) This gene encodes an enzyme that catalyzes the irreversible and NADPH-dependent reductive deamination of GMP to IMP. The protein also functions in the re-utilization of free intracellular bases and purine nucleosides.[provided by RefSeq, Oct 2009]

ENSG00000301361 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0852 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006877.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GMPR	NM_006877.4	MANE Select	c.465+1077G>T		intron	N/A	NP_006868.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GMPR	ENST00000259727.5	TSL:1 MANE Select	c.465+1077G>T		intron	N/A	ENSP00000259727.4
	ENSG00000301361	ENST00000778486.1		n.126-891C>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0747 AC: 11358 AN: 151976 Hom.: 434 Cov.: 31

Gnomad AFR AF: 0.0662

Gnomad AMI AF: 0.146

Gnomad AMR AF: 0.0523

Gnomad ASJ AF: 0.0793

Gnomad EAS AF: 0.000962

Gnomad SAS AF: 0.0686

Gnomad FIN AF: 0.0944

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.0871

Gnomad OTH AF: 0.0660

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0747 AC: 11362 AN: 152094 Hom.: 435 Cov.: 31 AF XY: 0.0729 AC XY: 5418 AN XY: 74350

African (AFR) AF: 0.0661 AC: 2744 AN: 41488

American (AMR) AF: 0.0522 AC: 798 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0793 AC: 275 AN: 3468

East Asian (EAS) AF: 0.000964 AC: 5 AN: 5186

South Asian (SAS) AF: 0.0682 AC: 328 AN: 4806

European-Finnish (FIN) AF: 0.0944 AC: 995 AN: 10542

Middle Eastern (MID) AF: 0.0884 AC: 26 AN: 294

European-Non Finnish (NFE) AF: 0.0871 AC: 5920 AN: 68002

Other (OTH) AF: 0.0653 AC: 138 AN: 2114

Alfa AF: 0.0828 Hom.: 994

Bravo AF: 0.0724

Asia WGS AF: 0.0240 AC: 84 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	6.7
DANN	Benign	0.80
PhyloP100		0.87
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10484358; hg19: chr6-16256043;