Variant 2-27086791-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_006488.3(KHK):c.-469A>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.521 in 152,656 control chromosomes in the GnomAD database, including 22,537 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.52 ( 22447 hom., cov: 34)

Exomes 𝑓: 0.56 ( 90 hom. )

Consequence

KHK
NM_006488.3 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.0440

Variant links:

Genes affected

KHK (HGNC:6315): (ketohexokinase) This gene encodes ketohexokinase that catalyzes conversion of fructose to fructose-1-phosphate. The product of this gene is the first enzyme with a specialized pathway that catabolizes dietary fructose. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]

KHK links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant 2-27086791-A-C is Benign according to our data. Variant chr2-27086791-A-C is described in ClinVar as [Benign]. Clinvar id is 335473.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.757 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KHK	NM_006488.3 linkuse as main transcript	c.-469A>C		5_prime_UTR_variant	1/8	ENST00000260598.10	NP_006479.1

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KHK	ENST00000260598.10 linkuse as main transcript	c.-469A>C	5_prime_UTR_variant	1/8	2	NM_006488.3	ENSP00000260598	P3	P50053-1
KHK	ENST00000260599.11 linkuse as main transcript	c.-469A>C	5_prime_UTR_variant	1/8	1		ENSP00000260599	A1	P50053-2
KHK	ENST00000490823.5 linkuse as main transcript	n.8A>C	non_coding_transcript_exon_variant	1/10	5
KHK	ENST00000429697.2 linkuse as main transcript		upstream_gene_variant		5		ENSP00000404741

Frequencies

GnomAD3 genomes

AF:

0.521

AC:

79186

AN:

152012

Hom.:

22445

Cov.:

show subpopulations

Gnomad AFR

AF:

0.301

Gnomad AMI

AF:

0.469

Gnomad AMR

AF:

0.443

Gnomad ASJ

AF:

0.597

Gnomad EAS

AF:

0.777

Gnomad SAS

AF:

0.685

Gnomad FIN

AF:

0.658

Gnomad MID

AF:

0.624

Gnomad NFE

AF:

0.616

Gnomad OTH

AF:

0.546

GnomAD4 exome

AF:

0.563

AC:

297

AN:

528

Hom.:

Cov.:

AF XY:

0.603

AC XY:

188

AN XY:

312

show subpopulations

Gnomad4 AFR exome

AF:

0.286

Gnomad4 AMR exome

AF:

0.438

Gnomad4 ASJ exome

AF:

0.600

Gnomad4 EAS exome

AF:

0.667

Gnomad4 SAS exome

AF:

0.614

Gnomad4 FIN exome

AF:

0.500

Gnomad4 NFE exome

AF:

0.542

Gnomad4 OTH exome

AF:

0.615

GnomAD4 genome

AF:

0.521

AC:

79194

AN:

152128

Hom.:

22447

Cov.:

AF XY:

0.525

AC XY:

39065

AN XY:

74386

show subpopulations

Gnomad4 AFR

AF:

0.300

Gnomad4 AMR

AF:

0.442

Gnomad4 ASJ

AF:

0.597

Gnomad4 EAS

AF:

0.777

Gnomad4 SAS

AF:

0.686

Gnomad4 FIN

AF:

0.658

Gnomad4 NFE

AF:

0.616

Gnomad4 OTH

AF:

0.543

Alfa

AF:

0.547

Hom.:

2965

Bravo

AF:

0.489

Asia WGS

AF:

0.672

AC:

2329

AN:

3466

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Essential fructosuria

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

DANN

Benign

0.58

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over