chr1-158612856-T-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_003126.4(SPTA1):c.7095A>G(p.Ala2365Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.542 in 1,613,310 control chromosomes in the GnomAD database, including 238,993 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.52 ( 21074 hom., cov: 31)

Exomes 𝑓: 0.54 ( 217919 hom. )

Consequence

SPTA1
NM_003126.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:13

Conservation

PhyloP100: -1.73

Publications

17 publications found

Variant links:

Genes affected

SPTA1 (HGNC:11272): (spectrin alpha, erythrocytic 1) This gene encodes a member of a family of molecular scaffold proteins that link the plasma membrane to the actin cytoskeleton and functions in the determination of cell shape, arrangement of transmembrane proteins, and organization of organelles. The encoded protein is primarily composed of 22 spectrin repeats which are involved in dimer formation. It forms a component of the erythrocyte plasma membrane. Mutations in this gene result in a variety of hereditary red blood cell disorders, including elliptocytosis-2, pyropoikilocytosis, and spherocytosis, type 3. [provided by RefSeq, Aug 2017]

SPTA1 Gene-Disease associations (from GenCC):

hereditary spherocytosis type 3
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae), Ambry Genetics, PanelApp Australia
elliptocytosis 2
Inheritance: AD Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Laboratory for Molecular Medicine, PanelApp Australia, Labcorp Genetics (formerly Invitae)
pyropoikilocytosis, hereditary
Inheritance: AR Classification: STRONG, MODERATE Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae), Ambry Genetics
hereditary elliptocytosis
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
hereditary spherocytosis
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

SPTA1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.73).

BP6

Variant 1-158612856-T-C is Benign according to our data. Variant chr1-158612856-T-C is described in ClinVar as Benign. ClinVar VariationId is 258958.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.73 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.605 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003126.4. 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
	SPTA1	NM_003126.4	MANE Select	c.7095A>G	p.Ala2365Ala	synonymous	Exon 51 of 52	NP_003117.2	P02549-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SPTA1	ENST00000643759.2	MANE Select	c.7095A>G	p.Ala2365Ala	synonymous	Exon 51 of 52	ENSP00000495214.1	P02549-1
SPTA1	ENST00000481212.5	TSL:3	n.536A>G		non_coding_transcript_exon	Exon 3 of 3
SPTA1	ENST00000498708.1	TSL:3	n.527A>G		non_coding_transcript_exon	Exon 5 of 5

Frequencies

GnomAD3 genomes

AF:

0.521

AC:

79168

AN:

151856

Hom.:

21048

Cov.:

show subpopulations

Gnomad AFR

AF:

0.423

Gnomad AMI

AF:

0.555

Gnomad AMR

AF:

0.544

Gnomad ASJ

AF:

0.570

Gnomad EAS

AF:

0.623

Gnomad SAS

AF:

0.432

Gnomad FIN

AF:

0.638

Gnomad MID

AF:

0.608

Gnomad NFE

AF:

0.553

Gnomad OTH

AF:

0.537

GnomAD2 exomes

AF:

0.542

AC:

134682

AN:

248610

AF XY:

0.539

show subpopulations

Gnomad AFR exome

AF:

0.423

Gnomad AMR exome

AF:

0.544

Gnomad ASJ exome

AF:

0.580

Gnomad EAS exome

AF:

0.611

Gnomad FIN exome

AF:

0.635

Gnomad NFE exome

AF:

0.555

Gnomad OTH exome

AF:

0.550

GnomAD4 exome

AF:

0.544

AC:

795007

AN:

1461336

Hom.:

217919

Cov.:

AF XY:

0.541

AC XY:

393337

AN XY:

726994

show subpopulations

African (AFR)

AF:

0.427

AC:

14297

AN:

33458

American (AMR)

AF:

0.545

AC:

24344

AN:

44682

Ashkenazi Jewish (ASJ)

AF:

0.578

AC:

15092

AN:

26126

East Asian (EAS)

AF:

0.599

AC:

23766

AN:

39694

South Asian (SAS)

AF:

0.430

AC:

37059

AN:

86244

European-Finnish (FIN)

AF:

0.630

AC:

33649

AN:

53398

Middle Eastern (MID)

AF:

0.530

AC:

3054

AN:

5766

European-Non Finnish (NFE)

AF:

0.549

AC:

610648

AN:

1111600

Other (OTH)

AF:

0.548

AC:

33098

AN:

60368

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

20278

40556

60834

81112

101390

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

17134

34268

51402

68536

85670

<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:

0.521

AC:

79243

AN:

151974

Hom.:

21074

Cov.:

AF XY:

0.527

AC XY:

39156

AN XY:

74272

show subpopulations

African (AFR)

AF:

0.423

AC:

17538

AN:

41468

American (AMR)

AF:

0.544

AC:

8302

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.570

AC:

1976

AN:

3466

East Asian (EAS)

AF:

0.623

AC:

3202

AN:

5138

South Asian (SAS)

AF:

0.433

AC:

2084

AN:

4816

European-Finnish (FIN)

AF:

0.638

AC:

6739

AN:

10558

Middle Eastern (MID)

AF:

0.606

AC:

177

AN:

292

European-Non Finnish (NFE)

AF:

0.553

AC:

37575

AN:

67950

Other (OTH)

AF:

0.542

AC:

1144

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1911

3822

5734

7645

9556

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

696

1392

2088

2784

3480

<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:

0.540

Hom.:

10008

Bravo

AF:

0.515

Asia WGS

AF:

0.559

AC:

1941

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (4)

not specified (3)

Elliptocytosis 2 (2)

Hereditary spherocytosis type 3 (2)

Pyropoikilocytosis, hereditary (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.73

CADD

Benign

4.3

(source)

DANN

Benign

0.58

PhyloP100

-1.7

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