dbSNP rs1880057: SGPL1:c.616-1555T>C (chr10-70866790-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_003901.4(SGPL1):c.616-1555T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.119 in 152,308 control chromosomes in the GnomAD database, including 1,346 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 0.12 ( 1346 hom., cov: 32)

Exomes 𝑓: 0.25 ( 0 hom. )

Consequence

SGPL1
NM_003901.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.38

Publications

1 publications found

Variant links:

Genes affected

SGPL1 (HGNC:10817): (sphingosine-1-phosphate lyase 1) Enables sphinganine-1-phosphate aldolase activity. Involved in apoptotic signaling pathway; fatty acid metabolic process; and sphingolipid metabolic process. Located in endoplasmic reticulum. Implicated in nephrotic syndrome type 14. [provided by Alliance of Genome Resources, Apr 2022]

SGPL1 Gene-Disease associations (from GenCC):

nephrotic syndrome 14
Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Ambry Genetics, ClinGen, PanelApp Australia, Labcorp Genetics (formerly Invitae)

SGPL1 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=-0.83).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.166 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003901.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
SGPL1	NM_003901.4	MANE Select	c.616-1555T>C	intron	N/A	NP_003892.2
SGPL1	NM_001438353.1		c.649-1555T>C	intron	N/A	NP_001425282.1
SGPL1	NM_001438354.1		c.616-1555T>C	intron	N/A	NP_001425283.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SGPL1	ENST00000373202.8	TSL:1 MANE Select	c.616-1555T>C	intron	N/A	ENSP00000362298.3	O95470
SGPL1	ENST00000697928.1		c.616-1555T>C	intron	N/A	ENSP00000513482.1	O95470
SGPL1	ENST00000697931.1		c.616-1555T>C	intron	N/A	ENSP00000513485.1	O95470

Frequencies

GnomAD3 genomes

AF:

0.119

AC:

18147

AN:

152186

Hom.:

1346

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0423

Gnomad AMI

AF:

0.112

Gnomad AMR

AF:

0.106

Gnomad ASJ

AF:

0.160

Gnomad EAS

AF:

0.0871

Gnomad SAS

AF:

0.0699

Gnomad FIN

AF:

0.150

Gnomad MID

AF:

0.108

Gnomad NFE

AF:

0.168

Gnomad OTH

AF:

0.125

GnomAD4 exome

AF:

0.250

AC:

AN:

Hom.:

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.250

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.119

AC:

18138

AN:

152304

Hom.:

1346

Cov.:

AF XY:

0.115

AC XY:

8550

AN XY:

74468

show subpopulations

African (AFR)

AF:

0.0421

AC:

1752

AN:

41584

American (AMR)

AF:

0.106

AC:

1616

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.160

AC:

556

AN:

3468

East Asian (EAS)

AF:

0.0866

AC:

449

AN:

5186

South Asian (SAS)

AF:

0.0689

AC:

333

AN:

4834

European-Finnish (FIN)

AF:

0.150

AC:

1590

AN:

10598

Middle Eastern (MID)

AF:

0.112

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.168

AC:

11445

AN:

68016

Other (OTH)

AF:

0.124

AC:

262

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

800

1599

2399

3198

3998

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

200

400

600

800

1000

<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:

0.152

Hom.:

981

Bravo

AF:

0.114

Asia WGS

AF:

0.0740

AC:

259

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.13

(source)

DANN

Benign

0.71

PhyloP100

-1.4

Mutation Taster

=100/0

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over