Variant rs11622977 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001355436.2(SPTB):c.6269+13C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.113 in 1,613,462 control chromosomes in the GnomAD database, including 12,992 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.16 ( 2927 hom., cov: 33)

Exomes 𝑓: 0.11 ( 10065 hom. )

Consequence

SPTB
NM_001355436.2 intron

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -1.62

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:

SPTB (HGNC:):

SPTB links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BP6

Variant 14-64767290-G-A is Benign according to our data. Variant chr14-64767290-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 257134.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-64767290-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.331 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.6269+13C>T		intron_variant		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.6269+13C>T		intron_variant			NM_001355436.2	ENSP00000495909.1		P11277-2

Frequencies

GnomAD3 genomes

AF:

0.165

AC:

25018

AN:

152034

Hom.:

2921

Cov.:

show subpopulations

Gnomad AFR

AF:

0.335

Gnomad AMI

AF:

0.0932

Gnomad AMR

AF:

0.100

Gnomad ASJ

AF:

0.103

Gnomad EAS

AF:

0.00692

Gnomad SAS

AF:

0.0643

Gnomad FIN

AF:

0.0787

Gnomad MID

AF:

0.123

Gnomad NFE

AF:

0.113

Gnomad OTH

AF:

0.139

GnomAD3 exomes

AF:

0.104

AC:

26102

AN:

251210

Hom.:

2015

AF XY:

0.0997

AC XY:

13543

AN XY:

135786

show subpopulations

Gnomad AFR exome

AF:

0.339

Gnomad AMR exome

AF:

0.0647

Gnomad ASJ exome

AF:

0.0929

Gnomad EAS exome

AF:

0.00913

Gnomad SAS exome

AF:

0.0698

Gnomad FIN exome

AF:

0.0825

Gnomad NFE exome

AF:

0.112

Gnomad OTH exome

AF:

0.0999

GnomAD4 exome

AF:

0.108

AC:

157941

AN:

1461310

Hom.:

10065

Cov.:

AF XY:

0.106

AC XY:

77279

AN XY:

727006

show subpopulations

Gnomad4 AFR exome

AF:

0.342

Gnomad4 AMR exome

AF:

0.0698

Gnomad4 ASJ exome

AF:

0.0985

Gnomad4 EAS exome

AF:

0.00557

Gnomad4 SAS exome

AF:

0.0687

Gnomad4 FIN exome

AF:

0.0854

Gnomad4 NFE exome

AF:

0.111

Gnomad4 OTH exome

AF:

0.111

GnomAD4 genome

AF:

0.165

AC:

25053

AN:

152152

Hom.:

2927

Cov.:

AF XY:

0.160

AC XY:

11924

AN XY:

74396

show subpopulations

Gnomad4 AFR

AF:

0.335

Gnomad4 AMR

AF:

0.0998

Gnomad4 ASJ

AF:

0.103

Gnomad4 EAS

AF:

0.00675

Gnomad4 SAS

AF:

0.0637

Gnomad4 FIN

AF:

0.0787

Gnomad4 NFE

AF:

0.113

Gnomad4 OTH

AF:

0.138

Alfa

AF:

0.120

Hom.:

854

Bravo

AF:

0.172

Asia WGS

AF:

0.0680

AC:

239

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -
Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Nov 27, 2023	- -
Likely 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

- -

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

-0.92

CADD

Benign

0.16

DANN

Benign

0.32

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