Variant 2-54558897-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_003128.3(SPTBN1):c.148+32331C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000157 in 1,612,108 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00016 ( 0 hom. )

Consequence

SPTBN1
NM_003128.3 intron

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.555

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 links:

SPTBN1 (HGNC:):

SPTBN1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.63).

BP6

Variant 2-54558897-C-A is Benign according to our data. Variant chr2-54558897-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 3349082.Status of the report is no_assertion_criteria_provided, 0 stars.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.000105 (16/152340) while in subpopulation SAS AF= 0.000207 (1/4826). AF 95% confidence interval is 0.000112. There are 0 homozygotes in gnomad4. There are 10 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 16 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPTBN1	NM_003128.3 linkuse as main transcript	c.148+32331C>A		intron_variant		ENST00000356805.9	NP_003119.2	Q01082-1B2ZZ89

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
SPTBN1	ENST00000356805.9 linkuse as main transcript	c.148+32331C>A	intron_variant	1	NM_003128.3	ENSP00000349259.4	Q01082-1
SPTBN1	ENST00000333896.5 linkuse as main transcript	c.109+10C>A	intron_variant	1		ENSP00000334156.5	Q01082-3
SPTBN1	ENST00000389980.7 linkuse as main transcript	c.148+32331C>A	intron_variant	1		ENSP00000374630.3	F8W6C1
SPTBN1	ENST00000615901.4 linkuse as main transcript	c.148+32331C>A	intron_variant	5			A0A087WUZ3

Frequencies

GnomAD3 genomes

AF:

0.000105

AC:

AN:

152222

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000191

Gnomad OTH

AF:

0.000956

GnomAD3 exomes

AF:

0.000130

AC:

AN:

246830

Hom.:

AF XY:

0.000142

AC XY:

AN XY:

133804

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000176

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000226

Gnomad OTH exome

AF:

0.000166

GnomAD4 exome

AF:

0.000162

AC:

237

AN:

1459768

Hom.:

Cov.:

AF XY:

0.000158

AC XY:

115

AN XY:

726052

show subpopulations

Gnomad4 AFR exome

AF:

0.0000599

Gnomad4 AMR exome

AF:

0.000202

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000465

Gnomad4 FIN exome

AF:

0.0000188

Gnomad4 NFE exome

AF:

0.000182

Gnomad4 OTH exome

AF:

0.000216

GnomAD4 genome

AF:

0.000105

AC:

AN:

152340

Hom.:

Cov.:

AF XY:

0.000134

AC XY:

AN XY:

74492

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000191

Gnomad4 OTH

AF:

0.000946

Alfa

AF:

0.0000427

Hom.:

Bravo

AF:

0.0000869

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

SPTBN1-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Mar 28, 2024

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.63

CADD

Benign

4.1

DANN

Benign

0.82

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.3

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over