14-64779244-A-G

Variant names:

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_001355436.2(SPTB):c.4476T>C(p.Leu1492Leu) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.259 in 1,602,920 control chromosomes in the GnomAD database, including 61,885 homozygotes. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.34 ( 11193 hom., cov: 32)

Exomes 𝑓: 0.25 ( 50692 hom. )

Consequence

SPTB
NM_001355436.2 splice_region, synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 0.0400

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 -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.42).

BP6

Variant 14-64779244-A-G is Benign according to our data. Variant chr14-64779244-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 257118.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-64779244-A-G is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.04 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.607 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPTB	NM_001355436.2 link	c.4476T>C	p.Leu1492Leu	splice_region_variant, synonymous_variant	Exon 22 of 36	ENST00000644917.1	NP_001342365.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SPTB	ENST00000644917.1 link	c.4476T>C	p.Leu1492Leu	splice_region_variant, synonymous_variant	Exon 22 of 36		NM_001355436.2	ENSP00000495909.1	P11277-2
SPTB	ENST00000553938.5 link	c.471T>C	p.Leu157Leu	splice_region_variant, synonymous_variant	Exon 3 of 18	1		ENSP00000451324.1	H0YJE6
SPTB	ENST00000389722.7 link	c.4476T>C	p.Leu1492Leu	splice_region_variant, synonymous_variant	Exon 21 of 35	2		ENSP00000374372.3	P11277-2
SPTB	ENST00000389720.4 link	c.4476T>C	p.Leu1492Leu	splice_region_variant, synonymous_variant	Exon 22 of 32	5		ENSP00000374370.4	P11277-1

Frequencies

GnomAD3 genomes

AF:

0.341

AC:

51806

AN:

151738

Hom.:

11166

Cov.:

show subpopulations

Gnomad AFR

AF:

0.613

Gnomad AMI

AF:

0.245

Gnomad AMR

AF:

0.209

Gnomad ASJ

AF:

0.262

Gnomad EAS

AF:

0.338

Gnomad SAS

AF:

0.382

Gnomad FIN

AF:

0.228

Gnomad MID

AF:

0.310

Gnomad NFE

AF:

0.228

Gnomad OTH

AF:

0.325

GnomAD3 exomes

AF:

0.267

AC:

66169

AN:

248078

Hom.:

10463

AF XY:

0.269

AC XY:

36060

AN XY:

134136

show subpopulations

Gnomad AFR exome

AF:

0.618

Gnomad AMR exome

AF:

0.136

Gnomad ASJ exome

AF:

0.260

Gnomad EAS exome

AF:

0.329

Gnomad SAS exome

AF:

0.373

Gnomad FIN exome

AF:

0.224

Gnomad NFE exome

AF:

0.228

Gnomad OTH exome

AF:

0.262

GnomAD4 exome

AF:

0.251

AC:

363768

AN:

1451064

Hom.:

50692

Cov.:

AF XY:

0.254

AC XY:

183048

AN XY:

722028

show subpopulations

Gnomad4 AFR exome

AF:

0.633

Gnomad4 AMR exome

AF:

0.145

Gnomad4 ASJ exome

AF:

0.267

Gnomad4 EAS exome

AF:

0.321

Gnomad4 SAS exome

AF:

0.366

Gnomad4 FIN exome

AF:

0.220

Gnomad4 NFE exome

AF:

0.231

Gnomad4 OTH exome

AF:

0.282

GnomAD4 genome

AF:

0.342

AC:

51871

AN:

151856

Hom.:

11193

Cov.:

AF XY:

0.340

AC XY:

25207

AN XY:

74226

show subpopulations

Gnomad4 AFR

AF:

0.613

Gnomad4 AMR

AF:

0.209

Gnomad4 ASJ

AF:

0.262

Gnomad4 EAS

AF:

0.337

Gnomad4 SAS

AF:

0.381

Gnomad4 FIN

AF:

0.228

Gnomad4 NFE

AF:

0.228

Gnomad4 OTH

AF:

0.321

Alfa

AF:

0.254

Hom.:

8432

Bravo

AF:

0.350

Asia WGS

AF:

0.370

AC:

1289

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 26, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Elliptocytosis

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Spherocytosis, Dominant

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Hereditary spherocytosis type 2

Benign:1

Jul 15, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.42

CADD

Benign

9.8

DANN

Benign

0.75

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