18-63328028-G-C

Position:

• chr18-63328028-G-C

Variant summary

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

The NM_002035.4(KDSR):​c.*3754C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.295 in 200,294 control chromosomes in the GnomAD database, including 9,319 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 0.30 (7446 hom., cov: 33)
  • Exomes 𝑓: 0.27 (1873 hom.)
• Consequence: KDSR NM_002035.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.85

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.407 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KDSR	NM_002035.4	c.*3754C>G		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	ENST00000645214.2	c.*3754C>G		3_prime_UTR_variant	10/10		NM_002035.4	ENSP00000494352	P1

Frequencies

GnomAD3 genomes AF: 0.303 AC: 45989 AN: 151864 Hom.: 7451 Cov.: 33

Gnomad AFR AF: 0.412

Gnomad AMI AF: 0.157

Gnomad AMR AF: 0.245

Gnomad ASJ AF: 0.254

Gnomad EAS AF: 0.331

Gnomad SAS AF: 0.396

Gnomad FIN AF: 0.254

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.254

Gnomad OTH AF: 0.268

GnomAD4 exome AF: 0.272 AC: 13147 AN: 48312 Hom.: 1873 Cov.: 0 AF XY: 0.271 AC XY: 6104 AN XY: 22514

Gnomad4 AFR exome AF: 0.396

Gnomad4 AMR exome AF: 0.227

Gnomad4 ASJ exome AF: 0.256

Gnomad4 EAS exome AF: 0.341

Gnomad4 SAS exome AF: 0.421

Gnomad4 FIN exome AF: 0.333

Gnomad4 NFE exome AF: 0.249

Gnomad4 OTH exome AF: 0.258

GnomAD4 genome AF: 0.303 AC: 46008 AN: 151982 Hom.: 7446 Cov.: 33 AF XY: 0.301 AC XY: 22369 AN XY: 74288

Gnomad4 AFR AF: 0.412

Gnomad4 AMR AF: 0.245

Gnomad4 ASJ AF: 0.254

Gnomad4 EAS AF: 0.332

Gnomad4 SAS AF: 0.395

Gnomad4 FIN AF: 0.254

Gnomad4 NFE AF: 0.254

Gnomad4 OTH AF: 0.266

Alfa AF: 0.147 Hom.: 264

Bravo AF: 0.300

Asia WGS AF: 0.351 AC: 1219 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	5.1
DANN	Benign	0.77

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: rs698708; hg19: chr18-60995261;