18-63328028-G-C

Variant names:

• chr18-63328028-G-C
• rs698708
• NM_002035.4:c.*3754C>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 13 publications found

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 Gene-Disease associations (from GenCC):

• erythrokeratodermia variabilis et progressiva 4

  Inheritance: AR Classification: DEFINITIVE, STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, G2P, Genomics England PanelApp
• erythrokeratodermia variabilis

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002035.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KDSR	NM_002035.4	MANE Select	c.*3754C>G		3_prime_UTR	Exon 10 of 10	NP_002026.1	Q06136-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KDSR	ENST00000645214.2	MANE Select	c.*3754C>G		3_prime_UTR	Exon 10 of 10	ENSP00000494352.1	Q06136-1
	KDSR	ENST00000882916.1		c.*3754C>G		3_prime_UTR	Exon 9 of 9	ENSP00000552975.1

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

African (AFR) AF: 0.396 AC: 803 AN: 2026

American (AMR) AF: 0.227 AC: 308 AN: 1356

Ashkenazi Jewish (ASJ) AF: 0.256 AC: 789 AN: 3088

East Asian (EAS) AF: 0.341 AC: 2632 AN: 7710

South Asian (SAS) AF: 0.421 AC: 176 AN: 418

European-Finnish (FIN) AF: 0.333 AC: 12 AN: 36

Middle Eastern (MID) AF: 0.234 AC: 68 AN: 290

European-Non Finnish (NFE) AF: 0.249 AC: 7330 AN: 29406

Other (OTH) AF: 0.258 AC: 1029 AN: 3982

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

African (AFR) AF: 0.412 AC: 17049 AN: 41410

American (AMR) AF: 0.245 AC: 3739 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.254 AC: 880 AN: 3470

East Asian (EAS) AF: 0.332 AC: 1715 AN: 5170

South Asian (SAS) AF: 0.395 AC: 1904 AN: 4824

European-Finnish (FIN) AF: 0.254 AC: 2680 AN: 10558

Middle Eastern (MID) AF: 0.241 AC: 71 AN: 294

European-Non Finnish (NFE) AF: 0.254 AC: 17266 AN: 67962

Other (OTH) AF: 0.266 AC: 561 AN: 2110

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	5.1
DANN	Benign	0.77
PhyloP100		1.8
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs698708; hg19: chr18-60995261;