Variant rs143820600 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_001355436.2(SPTB):c.6483C>T(p.Ser2161=) 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

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=-0.6).

BP6

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

BP7

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

BS1

Variant frequency is greater than expected in population mid. gnomad4_exome 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 gnomad4_exome. There are 1408 alleles in male gnomad4_exome subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 3 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPTB	NM_001355436.2 linkuse as main transcript	c.6483C>T	p.Ser2161=	synonymous_variant	33/36	ENST00000644917.1	NP_001342365.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPTB	ENST00000644917.1 linkuse as main transcript	c.6483C>T	p.Ser2161=	synonymous_variant	33/36		NM_001355436.2	ENSP00000495909	P1	P11277-2

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

GnomAD3 exomes

AF:

0.00351

AC:

883

AN:

251306

Hom.:

AF XY:

0.00361

AC XY:

490

AN XY:

135902

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 SAS exome

AF:

0.00359

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

Gnomad4 AFR exome

AF:

0.000388

Gnomad4 AMR exome

AF:

0.00181

Gnomad4 ASJ exome

AF:

0.0103

Gnomad4 EAS exome

AF:

0.000202

Gnomad4 SAS exome

AF:

0.00340

Gnomad4 FIN exome

AF:

0.0182

Gnomad4 NFE exome

AF:

0.000761

Gnomad4 OTH exome

AF:

0.00263

GnomAD4 genome

AF:

0.00234

AC:

356

AN:

152194

Hom.:

Cov.:

AF XY:

0.00298

AC XY:

222

AN XY:

74414

show subpopulations

Gnomad4 AFR

AF:

0.000434

Gnomad4 AMR

AF:

0.000981

Gnomad4 ASJ

AF:

0.00980

Gnomad4 EAS

AF:

0.000194

Gnomad4 SAS

AF:

0.00124

Gnomad4 FIN

AF:

0.0179

Gnomad4 NFE

AF:

0.00116

Gnomad4 OTH

AF:

0.00426

Alfa

AF:

0.00162

Hom.:

Bravo

AF:

0.00113

EpiCase

AF:

0.00158

EpiControl

AF:

0.00184

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	May 27, 2022	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Aug 01, 2024	SPTB: BP4, BP7, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.60

CADD

Benign

0.77

DANN

Benign

0.50

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