rs6810

Positions:

• chr18-63331168-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002035.4(KDSR):​c.*614T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.33 in 232,950 control chromosomes in the GnomAD database, including 15,330 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 0.32 (9568 hom., cov: 30)
  • Exomes 𝑓: 0.36 (5762 hom.)
• Consequence: KDSR NM_002035.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.421

Genes affected

KDSR (HGNC:4021): (3-ketodihydrosphingosine reductase) The protein encoded by this gene catalyzes the reduction of 3-ketodihydrosphingosine to dihydrosphingosine. The putative active site residues of the encoded protein are found on the cytosolic side of the endoplasmic reticulum membrane. A chromosomal rearrangement involving this gene is a cause of follicular lymphoma, also known as type II chronic lymphatic leukemia. The mutation of a conserved residue in the bovine ortholog causes spinal muscular atrophy. [provided by RefSeq, Jul 2008]

KDSR (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.432 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KDSR	NM_002035.4	c.*614T>C		3_prime_UTR_variant	10/10	ENST00000645214.2	NP_002026.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KDSR	ENST00000645214	c.*614T>C		3_prime_UTR_variant	10/10		NM_002035.4	ENSP00000494352.1

Frequencies

GnomAD3 genomes AF: 0.317 AC: 48083 AN: 151838 Hom.: 9566 Cov.: 30

Gnomad AFR AF: 0.0800

Gnomad AMI AF: 0.503

Gnomad AMR AF: 0.392

Gnomad ASJ AF: 0.353

Gnomad EAS AF: 0.0994

Gnomad SAS AF: 0.276

Gnomad FIN AF: 0.457

Gnomad MID AF: 0.389

Gnomad NFE AF: 0.436

Gnomad OTH AF: 0.351

GnomAD4 exome AF: 0.355 AC: 28756 AN: 80994 Hom.: 5762 Cov.: 0 AF XY: 0.357 AC XY: 13304 AN XY: 37260

Gnomad4 AFR exome AF: 0.0838

Gnomad4 AMR exome AF: 0.405

Gnomad4 ASJ exome AF: 0.345

Gnomad4 EAS exome AF: 0.116

Gnomad4 SAS exome AF: 0.254

Gnomad4 FIN exome AF: 0.424

Gnomad4 NFE exome AF: 0.430

Gnomad4 OTH exome AF: 0.359

GnomAD4 genome AF: 0.316 AC: 48088 AN: 151956 Hom.: 9568 Cov.: 30 AF XY: 0.318 AC XY: 23579 AN XY: 74248

Gnomad4 AFR AF: 0.0798

Gnomad4 AMR AF: 0.392

Gnomad4 ASJ AF: 0.353

Gnomad4 EAS AF: 0.0995

Gnomad4 SAS AF: 0.278

Gnomad4 FIN AF: 0.457

Gnomad4 NFE AF: 0.436

Gnomad4 OTH AF: 0.347

Alfa AF: 0.406 Hom.: 22370

Bravo AF: 0.303

Asia WGS AF: 0.174 AC: 606 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	11
DANN	Benign	0.83

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: rs6810; hg19: chr18-60998401;