dbSNP rs143820600: SPTB:p.Ser2161Ser (chr14-64753656-G-A) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_001355436.2(SPTB):c.6483C>T(p.Ser2161Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0019 in 1,613,600 control chromosomes in the GnomAD database, including 24 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0023 ( 3 hom., cov: 32)

Exomes 𝑓: 0.0019 ( 21 hom. )

Consequence

SPTB
NM_001355436.2 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.926

Publications

2 publications found

Variant links:

Genes affected

SPTB (HGNC:11274): (spectrin beta, erythrocytic) This locus encodes a member of the spectrin gene family. Spectrin proteins, along with ankyrin, play a role in cell membrane organization and stability. The protein encoded by this locus functions in stability of erythrocyte membranes, and mutations in this gene have been associated with spherocytosis type 2, hereditary elliptocytosis, and neonatal hemolytic anemia. Alternatively spliced transcript variants have been described. [provided by RefSeq, Nov 2009]

SPTB Gene-Disease associations (from GenCC):

hereditary spherocytosis type 2
Inheritance: AD Classification: STRONG Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae)
elliptocytosis 3
Inheritance: AR, AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia
hereditary elliptocytosis
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
hereditary spherocytosis
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

SPTB 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=-0.6).

BP6

Variant 14-64753656-G-A is Benign according to our data. Variant chr14-64753656-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 994185.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.926 with no splicing effect.

BS1

Variant frequency is greater than expected in population mid. GnomAdExome4 allele frequency = 0.00185 (2708/1461406) while in subpopulation MID AF = 0.0128 (74/5768). AF 95% confidence interval is 0.0105. There are 21 homozygotes in GnomAdExome4. There are 1408 alleles in the male GnomAdExome4 subpopulation. Median coverage is 31. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 3 AD,AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001355436.2. 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
	SPTB	NM_001355436.2	MANE Select	c.6483C>T	p.Ser2161Ser	synonymous	Exon 33 of 36	NP_001342365.1	P11277-2
	SPTB	NM_001024858.4		c.6483C>T	p.Ser2161Ser	synonymous	Exon 32 of 35	NP_001020029.1	P11277-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SPTB	ENST00000644917.1	MANE Select	c.6483C>T	p.Ser2161Ser	synonymous	Exon 33 of 36	ENSP00000495909.1	P11277-2
SPTB	ENST00000553938.5	TSL:1	c.2478C>T	p.Ser826Ser	synonymous	Exon 14 of 18	ENSP00000451324.1	H0YJE6
SPTB	ENST00000342835.9	TSL:1	n.220C>T		non_coding_transcript_exon	Exon 2 of 5

Frequencies

GnomAD3 genomes

AF:

0.00234

AC:

356

AN:

152076

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000435

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000982

Gnomad ASJ

AF:

0.00980

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00124

Gnomad FIN

AF:

0.0179

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.00116

Gnomad OTH

AF:

0.00430

GnomAD2 exomes

AF:

0.00351

AC:

883

AN:

251306

AF XY:

0.00361

show subpopulations

Gnomad AFR exome

AF:

0.000431

Gnomad AMR exome

AF:

0.00194

Gnomad ASJ exome

AF:

0.0105

Gnomad EAS exome

AF:

0.000381

Gnomad FIN exome

AF:

0.0171

Gnomad NFE exome

AF:

0.00163

Gnomad OTH exome

AF:

0.00522

GnomAD4 exome

AF:

0.00185

AC:

2708

AN:

1461406

Hom.:

Cov.:

AF XY:

0.00194

AC XY:

1408

AN XY:

726984

show subpopulations

African (AFR)

AF:

0.000388

AC:

AN:

33480

American (AMR)

AF:

0.00181

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0103

AC:

270

AN:

26136

East Asian (EAS)

AF:

0.000202

AC:

AN:

39700

South Asian (SAS)

AF:

0.00340

AC:

293

AN:

86256

European-Finnish (FIN)

AF:

0.0182

AC:

964

AN:

52942

Middle Eastern (MID)

AF:

0.0128

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000761

AC:

846

AN:

1112008

Other (OTH)

AF:

0.00263

AC:

159

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

208

416

624

832

1040

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

102

136

170

<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:

0.00234

AC:

356

AN:

152194

Hom.:

Cov.:

AF XY:

0.00298

AC XY:

222

AN XY:

74414

show subpopulations

African (AFR)

AF:

0.000434

AC:

AN:

41508

American (AMR)

AF:

0.000981

AC:

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.00980

AC:

AN:

3470

East Asian (EAS)

AF:

0.000194

AC:

AN:

5166

South Asian (SAS)

AF:

0.00124

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.0179

AC:

190

AN:

10598

Middle Eastern (MID)

AF:

0.0136

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00116

AC:

AN:

68020

Other (OTH)

AF:

0.00426

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

105

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

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

Alfa

AF:

0.00237

Hom.:

Bravo

AF:

0.00113

EpiCase

AF:

0.00158

EpiControl

AF:

0.00184

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.60

CADD

Benign

0.77

(source)

DANN

Benign

0.50

PhyloP100

-0.93

Mutation Taster

=99/1

polymorphism

(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

Computational scores

Splicing

Publications

Other links and lift over