rs698708

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr18-63328028-G-A
• chr18-63328028-G-C
• chr18-63328028-G-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_002035.4(KDSR):​c.*3754C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000206 in 48,460 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)
  • Exomes 𝑓: 0.000021 (0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).

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>T		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>T		3_prime_UTR	Exon 10 of 10	ENSP00000494352.1	Q06136-1
	KDSR	ENST00000882916.1		c.*3754C>T		3_prime_UTR	Exon 9 of 9	ENSP00000552975.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.0000206 AC: 1 AN: 48460 Hom.: 0 Cov.: 0 AF XY: 0.0000443 AC XY: 1 AN XY: 22570

African (AFR) AF: 0.00 AC: 0 AN: 2044

American (AMR) AF: 0.00 AC: 0 AN: 1358

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3098

East Asian (EAS) AF: 0.00 AC: 0 AN: 7742

South Asian (SAS) AF: 0.00 AC: 0 AN: 418

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 36

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 290

European-Non Finnish (NFE) AF: 0.0000339 AC: 1 AN: 29490

Other (OTH) AF: 0.00 AC: 0 AN: 3984

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 264

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	5.6
DANN	Benign	0.74
PhyloP100		1.8

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;