rs67760762

chr2-69359238-A-Gchr2-69359238-A-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001244710.2(GFPT1):c.408+30T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.379 in 1,216,722 control chromosomes in the GnomAD database, including 93,521 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.31 (9054 hom., cov: 32)
  • Exomes 𝑓: 0.39 (84467 hom.)
• Consequence: GFPT1 NM_001244710.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.553

Genes affected

GFPT1 (HGNC:4241): (glutamine--fructose-6-phosphate transaminase 1) This gene encodes the first and rate-limiting enzyme of the hexosamine pathway and controls the flux of glucose into the hexosamine pathway. The product of this gene catalyzes the formation of glucosamine 6-phosphate. [provided by RefSeq, Sep 2008]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 2-69359238-A-G is Benign according to our data. Variant chr2-69359238-A-G is described in ClinVar as [Benign]. Clinvar id is 258543.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-69359238-A-G is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.413 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GFPT1	NM_001244710.2	c.408+30T>C		intron_variant		ENST00000357308.9
GFPT1	NM_002056.4	c.408+30T>C		intron_variant
GFPT1	XM_017003801.2	c.483+30T>C		intron_variant
GFPT1	XM_017003802.3	c.483+30T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GFPT1	ENST00000357308.9	c.408+30T>C		intron_variant		5	NM_001244710.2
GFPT1	ENST00000361060.5	c.408+30T>C		intron_variant		1		P1
GFPT1	ENST00000674438.1	c.192+30T>C		intron_variant
GFPT1	ENST00000674507.1	c.408+30T>C		intron_variant

Frequencies

GnomAD3 genomes AF: 0.311 AC: 47295 AN: 151960 Hom.: 9042 Cov.: 32

Gnomad AFR AF: 0.0850

Gnomad AMI AF: 0.491

Gnomad AMR AF: 0.372

Gnomad ASJ AF: 0.531

Gnomad EAS AF: 0.200

Gnomad SAS AF: 0.338

Gnomad FIN AF: 0.374

Gnomad MID AF: 0.417

Gnomad NFE AF: 0.417

Gnomad OTH AF: 0.352

GnomAD3 exomes AF: 0.370 AC: 92875 AN: 250888 Hom.: 18674 AF XY: 0.375 AC XY: 50851 AN XY: 135608

Gnomad AFR exome AF: 0.0745

Gnomad AMR exome AF: 0.385

Gnomad ASJ exome AF: 0.551

Gnomad EAS exome AF: 0.215

Gnomad SAS exome AF: 0.328

Gnomad FIN exome AF: 0.383

Gnomad NFE exome AF: 0.424

Gnomad OTH exome AF: 0.408

GnomAD4 exome AF: 0.389 AC: 413765 AN: 1064642 Hom.: 84467 Cov.: 15 AF XY: 0.389 AC XY: 213123 AN XY: 548196

Gnomad4 AFR exome AF: 0.0706

Gnomad4 AMR exome AF: 0.384

Gnomad4 ASJ exome AF: 0.549

Gnomad4 EAS exome AF: 0.196

Gnomad4 SAS exome AF: 0.332

Gnomad4 FIN exome AF: 0.383

Gnomad4 NFE exome AF: 0.411

Gnomad4 OTH exome AF: 0.382

GnomAD4 genome AF: 0.311 AC: 47313 AN: 152080 Hom.: 9054 Cov.: 32 AF XY: 0.311 AC XY: 23121 AN XY: 74310

Gnomad4 AFR AF: 0.0848

Gnomad4 AMR AF: 0.372

Gnomad4 ASJ AF: 0.531

Gnomad4 EAS AF: 0.200

Gnomad4 SAS AF: 0.338

Gnomad4 FIN AF: 0.374

Gnomad4 NFE AF: 0.417

Gnomad4 OTH AF: 0.360

Alfa AF: 0.326 Hom.: 1609

Bravo AF: 0.301

Asia WGS AF: 0.288 AC: 1001 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 19, 2018

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Congenital myasthenic syndrome 12 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Aug 10, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	4.2
Dann	Benign	0.67
RBP_binding_hub_radar		0.67
RBP_regulation_power_radar		2.0

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

Publications

LitVar

Other links and lift over

dbSNP: rs67760762; hg19: chr2-69586370; COSMIC: COSV61946580; COSMIC: COSV61946580;