2-27099768-TCA-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBS1BS2

The NM_006488.3(KHK):​c.*24_*25delAC variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.019 in 1,612,704 control chromosomes in the GnomAD database, including 409 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.014 ( 28 hom., cov: 32)
Exomes 𝑓: 0.020 ( 381 hom. )

Consequence

KHK
NM_006488.3 3_prime_UTR

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.312
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]
CGREF1 (HGNC:16962): (cell growth regulator with EF-hand domain 1) Predicted to enable calcium ion binding activity. Predicted to be involved in negative regulation of cell population proliferation. Predicted to be located in extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP6
Variant 2-27099768-TCA-T is Benign according to our data. Variant chr2-27099768-TCA-T is described in ClinVar as [Likely_benign]. Clinvar id is 335500.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0138 (2096/152254) while in subpopulation SAS AF= 0.0411 (198/4822). AF 95% confidence interval is 0.0364. There are 28 homozygotes in gnomad4. There are 1020 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 28 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
KHKNM_006488.3 linkc.*24_*25delAC 3_prime_UTR_variant Exon 8 of 8 ENST00000260598.10 NP_006479.1 P50053-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
KHKENST00000260598.10 linkc.*24_*25delAC 3_prime_UTR_variant Exon 8 of 8 2 NM_006488.3 ENSP00000260598.5 P50053-1

Frequencies

GnomAD3 genomes
AF:
0.0138
AC:
2095
AN:
152136
Hom.:
28
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00294
Gnomad AMI
AF:
0.0440
Gnomad AMR
AF:
0.00857
Gnomad ASJ
AF:
0.0320
Gnomad EAS
AF:
0.000773
Gnomad SAS
AF:
0.0406
Gnomad FIN
AF:
0.0182
Gnomad MID
AF:
0.0222
Gnomad NFE
AF:
0.0186
Gnomad OTH
AF:
0.0110
GnomAD3 exomes
AF:
0.0185
AC:
4531
AN:
244720
Hom.:
52
AF XY:
0.0208
AC XY:
2766
AN XY:
132700
show subpopulations
Gnomad AFR exome
AF:
0.00254
Gnomad AMR exome
AF:
0.00699
Gnomad ASJ exome
AF:
0.0303
Gnomad EAS exome
AF:
0.000330
Gnomad SAS exome
AF:
0.0427
Gnomad FIN exome
AF:
0.0173
Gnomad NFE exome
AF:
0.0200
Gnomad OTH exome
AF:
0.0172
GnomAD4 exome
AF:
0.0195
AC:
28490
AN:
1460450
Hom.:
381
AF XY:
0.0204
AC XY:
14846
AN XY:
726400
show subpopulations
Gnomad4 AFR exome
AF:
0.00338
Gnomad4 AMR exome
AF:
0.00691
Gnomad4 ASJ exome
AF:
0.0315
Gnomad4 EAS exome
AF:
0.000126
Gnomad4 SAS exome
AF:
0.0423
Gnomad4 FIN exome
AF:
0.0166
Gnomad4 NFE exome
AF:
0.0192
Gnomad4 OTH exome
AF:
0.0206
GnomAD4 genome
AF:
0.0138
AC:
2096
AN:
152254
Hom.:
28
Cov.:
32
AF XY:
0.0137
AC XY:
1020
AN XY:
74444
show subpopulations
Gnomad4 AFR
AF:
0.00293
Gnomad4 AMR
AF:
0.00856
Gnomad4 ASJ
AF:
0.0320
Gnomad4 EAS
AF:
0.000775
Gnomad4 SAS
AF:
0.0411
Gnomad4 FIN
AF:
0.0182
Gnomad4 NFE
AF:
0.0186
Gnomad4 OTH
AF:
0.0109
Alfa
AF:
0.0178
Hom.:
3
Bravo
AF:
0.0124
Asia WGS
AF:
0.0150
AC:
54
AN:
3478

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Essential fructosuria Benign:1
Jun 14, 2016
Illumina Laboratory Services, Illumina
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

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.

Other links and lift over

dbSNP: rs370253620; hg19: chr2-27322636; API