2-27099768-TCA-T

Variant names:

• chr2-27099768-TCA-T
• rs370253620
• NM_006488.3:c.*24_*25delAC

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

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
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.312

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]

ACMG classification

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
KHK	NM_006488.3	c.*24_*25delAC		3_prime_UTR_variant	Exon 8 of 8	ENST00000260598.10	NP_006479.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KHK	ENST00000260598.10	c.*24_*25delAC		3_prime_UTR_variant	Exon 8 of 8	2	NM_006488.3	ENSP00000260598.5

Frequencies

GnomAD3 genomes AF: 0.0138 AC: 2095 AN: 152136 Hom.: 28 Cov.: 32

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

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

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

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

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

- -

Computational scores

Source: dbNSFP v4.3

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: rs370253620; hg19: chr2-27322636;