dbSNP rs11898505: SPTBN1:c.-48+902A>G (chr2-54457420-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_003128.3(SPTBN1):c.-48+902A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.758 in 152,478 control chromosomes in the GnomAD database, including 45,046 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 0.76 ( 44952 hom., cov: 31)

Exomes 𝑓: 0.63 ( 94 hom. )

Consequence

SPTBN1
NM_003128.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.855

Publications

45 publications found

Variant links:

Genes affected

SPTBN1 (HGNC:11275): (spectrin beta, non-erythrocytic 1) Spectrin is an actin crosslinking and molecular scaffold protein that links the plasma membrane to the actin cytoskeleton, and functions in the determination of cell shape, arrangement of transmembrane proteins, and organization of organelles. It is composed of two antiparallel dimers of alpha- and beta- subunits. This gene is one member of a family of beta-spectrin genes. The encoded protein contains an N-terminal actin-binding domain, and 17 spectrin repeats which are involved in dimer formation. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

SPTBN1 Gene-Disease associations (from GenCC):

developmental delay, impaired speech, and behavioral abnormalities
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, G2P

SPTBN1 links:

ENSG00000304706 (HGNC:):

ENSG00000304706 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=-0.86).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.926 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPTBN1	NM_003128.3 link	c.-48+902A>G		intron_variant	Intron 1 of 35	ENST00000356805.9	NP_003119.2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
SPTBN1	ENST00000356805.9 link	c.-48+902A>G	intron_variant	Intron 1 of 35	1	NM_003128.3	ENSP00000349259.4
SPTBN1	ENST00000389980.7 link	c.-48+113A>G	intron_variant	Intron 1 of 13	1		ENSP00000374630.3
ENSG00000304706	ENST00000805725.1 link	n.188+332T>C	intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes

AF:

0.759

AC:

115247

AN:

151904

Hom.:

44895

Cov.:

show subpopulations

Gnomad AFR

AF:

0.934

Gnomad AMI

AF:

0.716

Gnomad AMR

AF:

0.755

Gnomad ASJ

AF:

0.651

Gnomad EAS

AF:

0.875

Gnomad SAS

AF:

0.801

Gnomad FIN

AF:

0.763

Gnomad MID

AF:

0.709

Gnomad NFE

AF:

0.648

Gnomad OTH

AF:

0.719

GnomAD4 exome

AF:

0.625

AC:

285

AN:

456

Hom.:

AF XY:

0.592

AC XY:

167

AN XY:

282

show subpopulations

African (AFR)

AF:

1.00

AC:

AN:

American (AMR)

AF:

0.875

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.875

AC:

AN:

East Asian (EAS)

AF:

0.800

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.700

AC:

AN:

Middle Eastern (MID)

AF:

0.500

AC:

AN:

European-Non Finnish (NFE)

AF:

0.568

AC:

193

AN:

340

Other (OTH)

AF:

0.750

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

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

<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:

0.759

AC:

115362

AN:

152022

Hom.:

44952

Cov.:

AF XY:

0.767

AC XY:

56966

AN XY:

74294

show subpopulations

African (AFR)

AF:

0.934

AC:

38788

AN:

41526

American (AMR)

AF:

0.755

AC:

11546

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.651

AC:

2260

AN:

3470

East Asian (EAS)

AF:

0.875

AC:

4498

AN:

5142

South Asian (SAS)

AF:

0.800

AC:

3853

AN:

4814

European-Finnish (FIN)

AF:

0.763

AC:

8062

AN:

10560

Middle Eastern (MID)

AF:

0.697

AC:

205

AN:

294

European-Non Finnish (NFE)

AF:

0.648

AC:

43982

AN:

67908

Other (OTH)

AF:

0.719

AC:

1515

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1327

2655

3982

5310

6637

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

844

1688

2532

3376

4220

<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:

0.681

Hom.:

140004

Bravo

AF:

0.765

Asia WGS

AF:

0.844

AC:

2934

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

(source)

DANN

Benign

0.54

PhyloP100

-0.85

PromoterAI

-0.0066

Neutral

(source)

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over