Variant 14-64801382-A-G 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.666T>C(p.Phe222=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00853 in 1,614,164 control chromosomes in the GnomAD database, including 313 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.019 ( 74 hom., cov: 33)

Exomes 𝑓: 0.0074 ( 239 hom. )

Consequence

SPTB
NM_001355436.2 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.374

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:

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=-0.58).

BP6

Variant 14-64801382-A-G is Benign according to our data. Variant chr14-64801382-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 257136.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-64801382-A-G is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.374 with no splicing effect.

BA1

GnomAdExome4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0599 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SPTB	NM_001355436.2 linkuse as main transcript	c.666T>C	p.Phe222=	synonymous_variant	7/36	ENST00000644917.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SPTB	ENST00000644917.1 linkuse as main transcript	c.666T>C	p.Phe222=	synonymous_variant	7/36		NM_001355436.2	P1	P11277-2
SPTB	ENST00000389722.7 linkuse as main transcript	c.666T>C	p.Phe222=	synonymous_variant	6/35	2		P1	P11277-2
SPTB	ENST00000389720.4 linkuse as main transcript	c.666T>C	p.Phe222=	synonymous_variant	7/32	5			P11277-1

Frequencies

GnomAD3 genomes

AF:

0.0192

AC:

2925

AN:

152230

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0430

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0398

Gnomad ASJ

AF:

0.0210

Gnomad EAS

AF:

0.0324

Gnomad SAS

AF:

0.0240

Gnomad FIN

AF:

0.000565

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00179

Gnomad OTH

AF:

0.0224

GnomAD3 exomes

AF:

0.0185

AC:

4653

AN:

251442

Hom.:

139

AF XY:

0.0165

AC XY:

2240

AN XY:

135902

show subpopulations

Gnomad AFR exome

AF:

0.0436

Gnomad AMR exome

AF:

0.0625

Gnomad ASJ exome

AF:

0.0258

Gnomad EAS exome

AF:

0.0234

Gnomad SAS exome

AF:

0.0257

Gnomad FIN exome

AF:

0.000832

Gnomad NFE exome

AF:

0.00178

Gnomad OTH exome

AF:

0.0135

GnomAD4 exome

AF:

0.00742

AC:

10843

AN:

1461816

Hom.:

239

Cov.:

AF XY:

0.00758

AC XY:

5511

AN XY:

727204

show subpopulations

Gnomad4 AFR exome

AF:

0.0451

Gnomad4 AMR exome

AF:

0.0619

Gnomad4 ASJ exome

AF:

0.0270

Gnomad4 EAS exome

AF:

0.0349

Gnomad4 SAS exome

AF:

0.0259

Gnomad4 FIN exome

AF:

0.000880

Gnomad4 NFE exome

AF:

0.00137

Gnomad4 OTH exome

AF:

0.0105

GnomAD4 genome

AF:

0.0192

AC:

2930

AN:

152348

Hom.:

Cov.:

AF XY:

0.0192

AC XY:

1431

AN XY:

74508

show subpopulations

Gnomad4 AFR

AF:

0.0429

Gnomad4 AMR

AF:

0.0400

Gnomad4 ASJ

AF:

0.0210

Gnomad4 EAS

AF:

0.0326

Gnomad4 SAS

AF:

0.0236

Gnomad4 FIN

AF:

0.000565

Gnomad4 NFE

AF:

0.00179

Gnomad4 OTH

AF:

0.0222

Alfa

AF:

0.00795

Hom.:

Bravo

AF:

0.0253

Asia WGS

AF:

0.0360

AC:

124

AN:

3478

EpiCase

AF:

0.00185

EpiControl

AF:

0.00213

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 24, 2024	- -
Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Oct 16, 2023	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Elliptocytosis

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Spherocytosis, Dominant

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.58

CADD

Benign

8.4

DANN

Benign

0.74

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

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