Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The ENST00000372739.7(SPTAN1):c.5085A>G(p.Leu1695Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.997 in 1,614,244 control chromosomes in the GnomAD database, including 803,113 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. L1695L) has been classified as Benign.

Frequency

Genomes: 𝑓 0.99 ( 74104 hom., cov: 34)

Exomes 𝑓: 1.0 ( 729009 hom. )

Consequence

SPTAN1
ENST00000372739.7 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 3.23

Publications

20 publications found

Variant links:

Genes affected

SPTAN1 (HGNC:11273): (spectrin alpha, non-erythrocytic 1) Spectrins are a family of filamentous cytoskeletal proteins that function as essential scaffold proteins that stabilize the plasma membrane and organize intracellular organelles. Spectrins are composed of alpha and beta dimers that associate to form tetramers linked in a head-to-head arrangement. This gene encodes an alpha spectrin that is specifically expressed in nonerythrocytic cells. The encoded protein has been implicated in other cellular functions including DNA repair and cell cycle regulation. Mutations in this gene are the cause of early infantile epileptic encephalopathy-5. Alternate splicing results in multiple transcript variants.[provided by RefSeq, Sep 2010]

SPTAN1 Gene-Disease associations (from GenCC):

developmental and epileptic encephalopathy, 5
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine
genetic developmental and epileptic encephalopathy
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
infantile spasms
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

SPTAN1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.43).

BP6

Variant 9-128613422-A-G is Benign according to our data. Variant chr9-128613422-A-G is described in ClinVar as Benign. ClinVar VariationId is 1166053.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=3.23 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.993 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000372739.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
SPTAN1	NM_001130438.3	MANE Select	c.5085A>G	p.Leu1695Leu	synonymous	Exon 40 of 57	NP_001123910.1
SPTAN1	NM_001375318.1		c.5121A>G	p.Leu1707Leu	synonymous	Exon 41 of 59	NP_001362247.1
SPTAN1	NM_001375310.1		c.5085A>G	p.Leu1695Leu	synonymous	Exon 40 of 58	NP_001362239.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
SPTAN1	ENST00000372739.7	TSL:1 MANE Select	c.5085A>G	p.Leu1695Leu	synonymous	Exon 40 of 57	ENSP00000361824.4
SPTAN1	ENST00000372731.8	TSL:1	c.5070A>G	p.Leu1690Leu	synonymous	Exon 39 of 56	ENSP00000361816.4
SPTAN1	ENST00000358161.9	TSL:1	c.5010A>G	p.Leu1670Leu	synonymous	Exon 38 of 55	ENSP00000350882.6

Frequencies

GnomAD3 genomes

AF:

0.986

AC:

150119

AN:

152232

Hom.:

74056

Cov.:

show subpopulations

Gnomad AFR

AF:

0.952

Gnomad AMI

AF:

1.00

Gnomad AMR

AF:

0.995

Gnomad ASJ

AF:

1.00

Gnomad EAS

AF:

1.00

Gnomad SAS

AF:

1.00

Gnomad FIN

AF:

1.00

Gnomad MID

AF:

1.00

Gnomad NFE

AF:

1.00

Gnomad OTH

AF:

0.991

GnomAD2 exomes

AF:

0.997

AC:

250551

AN:

251416

AF XY:

0.998

show subpopulations

Gnomad AFR exome

AF:

0.954

Gnomad AMR exome

AF:

0.998

Gnomad ASJ exome

AF:

1.00

Gnomad EAS exome

AF:

1.00

Gnomad FIN exome

AF:

1.00

Gnomad NFE exome

AF:

1.00

Gnomad OTH exome

AF:

0.998

GnomAD4 exome

AF:

0.999

AC:

1459916

AN:

1461894

Hom.:

729009

Cov.:

AF XY:

0.999

AC XY:

726432

AN XY:

727248

show subpopulations

African (AFR)

AF:

0.953

AC:

31919

AN:

33480

American (AMR)

AF:

0.997

AC:

44596

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

1.00

AC:

26136

AN:

26136

East Asian (EAS)

AF:

1.00

AC:

39700

AN:

39700

South Asian (SAS)

AF:

1.00

AC:

86247

AN:

86258

European-Finnish (FIN)

AF:

1.00

AC:

53420

AN:

53420

Middle Eastern (MID)

AF:

0.998

AC:

5759

AN:

5768

European-Non Finnish (NFE)

AF:

1.00

AC:

1111919

AN:

1112012

Other (OTH)

AF:

0.997

AC:

60220

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

125

250

376

501

626

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

21672

43344

65016

86688

108360

<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:

0.986

AC:

150225

AN:

152350

Hom.:

74104

Cov.:

AF XY:

0.986

AC XY:

73465

AN XY:

74496

show subpopulations

African (AFR)

AF:

0.952

AC:

39568

AN:

41582

American (AMR)

AF:

0.995

AC:

15225

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

1.00

AC:

3470

AN:

3470

East Asian (EAS)

AF:

1.00

AC:

5182

AN:

5182

South Asian (SAS)

AF:

1.00

AC:

4824

AN:

4824

European-Finnish (FIN)

AF:

1.00

AC:

10628

AN:

10628

Middle Eastern (MID)

AF:

1.00

AC:

294

AN:

294

European-Non Finnish (NFE)

AF:

1.00

AC:

68027

AN:

68042

Other (OTH)

AF:

0.991

AC:

2095

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

105

210

315

420

525

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:

0.993

Hom.:

33508

Bravo

AF:

0.984

Asia WGS

AF:

0.999

AC:

3474

AN:

3478

EpiCase

AF:

1.00

EpiControl

AF:

1.00

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (3)

Developmental and epileptic encephalopathy (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.43

CADD

Benign

8.6

(source)

DANN

Benign

0.72

PhyloP100

3.2

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over