dbSNP rs184566: SPNS2:c.370+91T>C (chr17-4499508-T-C) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001124758.3(SPNS2):c.370+91T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 1 in 869,352 control chromosomes in the GnomAD database, including 434,333 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 1.0 ( 75830 hom., cov: 30)

Exomes 𝑓: 1.0 ( 358503 hom. )

Consequence

SPNS2
NM_001124758.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.954

Publications

4 publications found

Variant links:

Genes affected

SPNS2 (HGNC:26992): (SPNS lysolipid transporter 2, sphingosine-1-phosphate) The protein encoded by this gene is a transporter of sphingosine 1-phosphate, a secreted lipid that is important in cardiovascular, immunological, and neural development. Defects in this gene are a cause of early onset progressive hearing loss. [provided by RefSeq, Jul 2016]

SPNS2 links:

SPNS2-AS1 (HGNC:55787): (SPNS2 antisense RNA 1)

SPNS2-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.76).

BP6

Variant 17-4499508-T-C is Benign according to our data. Variant chr17-4499508-T-C is described in ClinVar as Benign. ClinVar VariationId is 1279916.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.994 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001124758.3. 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
	SPNS2	NM_001124758.3	MANE Select	c.370+91T>C		intron	N/A	NP_001118230.1	Q8IVW8

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SPNS2	ENST00000329078.8	TSL:1 MANE Select	c.370+91T>C	intron	N/A	ENSP00000333292.3	Q8IVW8
SPNS2	ENST00000947403.1		c.370+91T>C	intron	N/A	ENSP00000617462.1
SPNS2	ENST00000932033.1		c.370+91T>C	intron	N/A	ENSP00000602092.1

Frequencies

GnomAD3 genomes

AF:

0.999

AC:

151759

AN:

151974

Hom.:

75772

Cov.:

show subpopulations

Gnomad AFR

AF:

0.995

Gnomad AMI

AF:

1.00

Gnomad AMR

AF:

1.00

Gnomad ASJ

AF:

1.00

Gnomad EAS

AF:

0.998

Gnomad SAS

AF:

1.00

Gnomad FIN

AF:

1.00

Gnomad MID

AF:

0.997

Gnomad NFE

AF:

1.00

Gnomad OTH

AF:

1.00

GnomAD4 exome

AF:

1.00

AC:

717133

AN:

717260

Hom.:

358503

Cov.:

AF XY:

1.00

AC XY:

355474

AN XY:

355522

show subpopulations

African (AFR)

AF:

0.996

AC:

14588

AN:

14648

American (AMR)

AF:

1.00

AC:

8544

AN:

8544

Ashkenazi Jewish (ASJ)

AF:

1.00

AC:

12930

AN:

12930

East Asian (EAS)

AF:

1.00

AC:

24711

AN:

24722

South Asian (SAS)

AF:

1.00

AC:

33406

AN:

33408

European-Finnish (FIN)

AF:

1.00

AC:

26566

AN:

26566

Middle Eastern (MID)

AF:

1.00

AC:

2391

AN:

2392

European-Non Finnish (NFE)

AF:

1.00

AC:

561754

AN:

561774

Other (OTH)

AF:

0.999

AC:

32243

AN:

32276

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.521

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10158

20316

30474

40632

50790

<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:

0.999

AC:

151876

AN:

152092

Hom.:

75830

Cov.:

AF XY:

0.999

AC XY:

74241

AN XY:

74338

show subpopulations

African (AFR)

AF:

0.995

AC:

41308

AN:

41502

American (AMR)

AF:

1.00

AC:

15299

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

1.00

AC:

3472

AN:

3472

East Asian (EAS)

AF:

0.998

AC:

5072

AN:

5082

South Asian (SAS)

AF:

1.00

AC:

4822

AN:

4822

European-Finnish (FIN)

AF:

1.00

AC:

10620

AN:

10620

Middle Eastern (MID)

AF:

0.997

AC:

293

AN:

294

European-Non Finnish (NFE)

AF:

1.00

AC:

67965

AN:

67968

Other (OTH)

AF:

1.00

AC:

2113

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

914

1828

2742

3656

4570

<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:

1.00

Hom.:

3328

Bravo

AF:

0.998

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

9.1

(source)

DANN

Benign

0.57

PhyloP100

0.95

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