Genetic Variant KDSR:c.-69A>C (chr18-63367187-T-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_002035.4(KDSR):c.-69A>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.237 in 783,750 control chromosomes in the GnomAD database, including 28,841 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 0.34 ( 12158 hom., cov: 32)

Exomes 𝑓: 0.21 ( 16683 hom. )

Consequence

KDSR
NM_002035.4 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.549

Publications

15 publications found

Variant links:

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 links:

KDSR-DT (HGNC:55299): (KDSR divergent transcript)

KDSR-DT links:

LOC124904317 (HGNC:):

LOC124904317 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.75).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.672 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
KDSR	NM_002035.4 link	c.-69A>C	5_prime_UTR_variant	Exon 1 of 10	ENST00000645214.2	NP_002026.1	Q06136-1A0A024R292
KDSR-DT	NR_186602.1 link	n.-137T>G	upstream_gene_variant
LOC124904317	XR_007066400.1 link	n.-187A>C	upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KDSR	ENST00000645214.2 link	c.-69A>C		5_prime_UTR_variant	Exon 1 of 10		NM_002035.4	ENSP00000494352.1		Q06136-1

Frequencies

GnomAD3 genomes

AF:

0.340

AC:

51366

AN:

151152

Hom.:

12120

Cov.:

show subpopulations

Gnomad AFR

AF:

0.678

Gnomad AMI

AF:

0.154

Gnomad AMR

AF:

0.247

Gnomad ASJ

AF:

0.236

Gnomad EAS

AF:

0.300

Gnomad SAS

AF:

0.152

Gnomad FIN

AF:

0.200

Gnomad MID

AF:

0.309

Gnomad NFE

AF:

0.201

Gnomad OTH

AF:

0.310

GnomAD4 exome

AF:

0.212

AC:

134207

AN:

632490

Hom.:

16683

Cov.:

AF XY:

0.210

AC XY:

64550

AN XY:

306850

show subpopulations

African (AFR)

AF:

0.695

AC:

8842

AN:

12730

American (AMR)

AF:

0.207

AC:

1401

AN:

6758

Ashkenazi Jewish (ASJ)

AF:

0.225

AC:

2265

AN:

10076

East Asian (EAS)

AF:

0.262

AC:

5690

AN:

21722

South Asian (SAS)

AF:

0.143

AC:

1560

AN:

10904

European-Finnish (FIN)

AF:

0.192

AC:

6056

AN:

31540

Middle Eastern (MID)

AF:

0.266

AC:

572

AN:

2154

European-Non Finnish (NFE)

AF:

0.199

AC:

101325

AN:

509472

Other (OTH)

AF:

0.239

AC:

6496

AN:

27134

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

4408

8816

13225

17633

22041

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3734

7468

11202

14936

18670

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.340

AC:

51453

AN:

151260

Hom.:

12158

Cov.:

AF XY:

0.335

AC XY:

24765

AN XY:

73914

show subpopulations

African (AFR)

AF:

0.679

AC:

28057

AN:

41350

American (AMR)

AF:

0.247

AC:

3752

AN:

15206

Ashkenazi Jewish (ASJ)

AF:

0.236

AC:

817

AN:

3468

East Asian (EAS)

AF:

0.299

AC:

1528

AN:

5104

South Asian (SAS)

AF:

0.151

AC:

731

AN:

4826

European-Finnish (FIN)

AF:

0.200

AC:

2061

AN:

10318

Middle Eastern (MID)

AF:

0.305

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.201

AC:

13628

AN:

67694

Other (OTH)

AF:

0.310

AC:

650

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1404

2808

4212

5616

7020

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

456

912

1368

1824

2280

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.267

Hom.:

980

Bravo

AF:

0.364

Asia WGS

AF:

0.246

AC:

840

AN:

3416

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.75

CADD

Benign

(source)

DANN

Benign

0.77

PhyloP100

-0.55

PromoterAI

0.074

Neutral

(source)

Mutation Taster

=300/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over