18-63331168-A-G

Variant names:

• chr18-63331168-A-G
• rs6810
• NM_002035.4:c.*614T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 14 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=-0.66).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.432 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.*614T>C		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.*614T>C		3_prime_UTR	Exon 10 of 10	ENSP00000494352.1	Q06136-1
	KDSR	ENST00000951441.1		c.*614T>C		3_prime_UTR	Exon 11 of 11	ENSP00000621500.1
	KDSR	ENST00000882920.1		c.*614T>C		3_prime_UTR	Exon 10 of 10	ENSP00000552979.1

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

African (AFR) AF: 0.0838 AC: 327 AN: 3900

American (AMR) AF: 0.405 AC: 1010 AN: 2496

Ashkenazi Jewish (ASJ) AF: 0.345 AC: 1765 AN: 5120

East Asian (EAS) AF: 0.116 AC: 1322 AN: 11402

South Asian (SAS) AF: 0.254 AC: 178 AN: 700

European-Finnish (FIN) AF: 0.424 AC: 28 AN: 66

Middle Eastern (MID) AF: 0.398 AC: 196 AN: 492

European-Non Finnish (NFE) AF: 0.430 AC: 21499 AN: 50050

Other (OTH) AF: 0.359 AC: 2431 AN: 6768

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

African (AFR) AF: 0.0798 AC: 3311 AN: 41514

American (AMR) AF: 0.392 AC: 5976 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.353 AC: 1225 AN: 3470

East Asian (EAS) AF: 0.0995 AC: 514 AN: 5168

South Asian (SAS) AF: 0.278 AC: 1336 AN: 4800

European-Finnish (FIN) AF: 0.457 AC: 4799 AN: 10512

Middle Eastern (MID) AF: 0.394 AC: 115 AN: 292

European-Non Finnish (NFE) AF: 0.436 AC: 29623 AN: 67938

Other (OTH) AF: 0.347 AC: 731 AN: 2108

Alfa AF: 0.384 Hom.: 31975

Bravo AF: 0.303

Asia WGS AF: 0.174 AC: 606 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	11
DANN	Benign	0.83
PhyloP100		0.42
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: rs6810; hg19: chr18-60998401;