Variant chr14-64749402-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001355436.2(SPTB):c.6891G>A(p.Ala2297Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0697 in 1,607,956 control chromosomes in the GnomAD database, including 5,278 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.11 ( 1373 hom., cov: 32)

Exomes 𝑓: 0.066 ( 3905 hom. )

Consequence

SPTB
NM_001355436.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.40

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 links:

PLEKHG3 (HGNC:20364): (pleckstrin homology and RhoGEF domain containing G3) Predicted to enable guanyl-nucleotide exchange factor activity. Predicted to be involved in regulation of small GTPase mediated signal transduction. Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

PLEKHG3 links:

SPTB (HGNC:):

SPTB links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.53).

BP6

Variant 14-64749402-C-T is Benign according to our data. Variant chr14-64749402-C-T is described in ClinVar as [Benign]. Clinvar id is 257137.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-64749402-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-1.4 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.222 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPTB	NM_001355436.2 linkuse as main transcript	c.6891G>A	p.Ala2297Ala	synonymous_variant	36/36	ENST00000644917.1	NP_001342365.1
PLEKHG3	NM_001308147.2 linkuse as main transcript	c.*5699C>T		3_prime_UTR_variant	17/17	ENST00000247226.13	NP_001295076.1	A1L390-1A0A2X0SFH4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPTB	ENST00000644917.1 linkuse as main transcript	c.6891G>A	p.Ala2297Ala	synonymous_variant	36/36		NM_001355436.2	ENSP00000495909.1		P11277-2
PLEKHG3	ENST00000247226.13 linkuse as main transcript	c.*5699C>T		3_prime_UTR_variant	17/17	1	NM_001308147.2	ENSP00000247226.8		A1L390-1

Frequencies

GnomAD3 genomes

AF:

0.106

AC:

16180

AN:

152122

Hom.:

1368

Cov.:

show subpopulations

Gnomad AFR

AF:

0.226

Gnomad AMI

AF:

0.00548

Gnomad AMR

AF:

0.0437

Gnomad ASJ

AF:

0.0340

Gnomad EAS

AF:

0.0366

Gnomad SAS

AF:

0.0606

Gnomad FIN

AF:

0.103

Gnomad MID

AF:

0.0287

Gnomad NFE

AF:

0.0627

Gnomad OTH

AF:

0.0890

GnomAD3 exomes

AF:

0.0667

AC:

16191

AN:

242730

Hom.:

858

AF XY:

0.0649

AC XY:

8578

AN XY:

132188

show subpopulations

Gnomad AFR exome

AF:

0.233

Gnomad AMR exome

AF:

0.0252

Gnomad ASJ exome

AF:

0.0332

Gnomad EAS exome

AF:

0.0334

Gnomad SAS exome

AF:

0.0644

Gnomad FIN exome

AF:

0.0953

Gnomad NFE exome

AF:

0.0610

Gnomad OTH exome

AF:

0.0565

GnomAD4 exome

AF:

0.0659

AC:

95933

AN:

1455716

Hom.:

3905

Cov.:

AF XY:

0.0654

AC XY:

47356

AN XY:

724318

show subpopulations

Gnomad4 AFR exome

AF:

0.238

Gnomad4 AMR exome

AF:

0.0271

Gnomad4 ASJ exome

AF:

0.0332

Gnomad4 EAS exome

AF:

0.0427

Gnomad4 SAS exome

AF:

0.0630

Gnomad4 FIN exome

AF:

0.0962

Gnomad4 NFE exome

AF:

0.0627

Gnomad4 OTH exome

AF:

0.0704

GnomAD4 genome

AF:

0.107

AC:

16219

AN:

152240

Hom.:

1373

Cov.:

AF XY:

0.106

AC XY:

7915

AN XY:

74434

show subpopulations

Gnomad4 AFR

AF:

0.226

Gnomad4 AMR

AF:

0.0437

Gnomad4 ASJ

AF:

0.0340

Gnomad4 EAS

AF:

0.0367

Gnomad4 SAS

AF:

0.0604

Gnomad4 FIN

AF:

0.103

Gnomad4 NFE

AF:

0.0627

Gnomad4 OTH

AF:

0.0881

Alfa

AF:

0.0640

Hom.:

274

Bravo

AF:

0.106

Asia WGS

AF:

0.0650

AC:

227

AN:

3478

EpiCase

AF:

0.0593

EpiControl

AF:

0.0566

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Nov 22, 2023	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.53

CADD

Benign

3.7

DANN

Benign

0.92

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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