rs7142689

chr14-64769735-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001355436.2(SPTB):c.5799-7C>T variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.112 in 1,613,866 control chromosomes in the GnomAD database, including 12,813 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.16 (2852 hom., cov: 33)
  • Exomes 𝑓: 0.11 (9961 hom.)
• Consequence: SPTB NM_001355436.2 splice_region, splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.00001448
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 1.25

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 14-64769735-G-A is Benign according to our data. Variant chr14-64769735-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 257130.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-64769735-G-A is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.323 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SPTB	NM_001355436.2	c.5799-7C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000644917.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SPTB	ENST00000644917.1	c.5799-7C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant			NM_001355436.2	P1
SPTB	ENST00000553938.5	c.1794-7C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1
SPTB	ENST00000389720.4	c.5799-7C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		5
SPTB	ENST00000389722.7	c.5799-7C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		2		P1

Frequencies

GnomAD3 genomes AF: 0.161 AC: 24551 AN: 152042 Hom.: 2835 Cov.: 33

Gnomad AFR AF: 0.327

Gnomad AMI AF: 0.0932

Gnomad AMR AF: 0.0992

Gnomad ASJ AF: 0.103

Gnomad EAS AF: 0.00425

Gnomad SAS AF: 0.0354

Gnomad FIN AF: 0.0789

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.114

Gnomad OTH AF: 0.132

GnomAD3 exomes AF: 0.0992 AC: 24938 AN: 251318 Hom.: 1917 AF XY: 0.0938 AC XY: 12738 AN XY: 135864

Gnomad AFR exome AF: 0.330

Gnomad AMR exome AF: 0.0628

Gnomad ASJ exome AF: 0.0923

Gnomad EAS exome AF: 0.00544

Gnomad SAS exome AF: 0.0391

Gnomad FIN exome AF: 0.0826

Gnomad NFE exome AF: 0.113

Gnomad OTH exome AF: 0.0962

GnomAD4 exome AF: 0.107 AC: 155960 AN: 1461704 Hom.: 9961 Cov.: 33 AF XY: 0.104 AC XY: 75760 AN XY: 727174

Gnomad4 AFR exome AF: 0.339

Gnomad4 AMR exome AF: 0.0684

Gnomad4 ASJ exome AF: 0.0983

Gnomad4 EAS exome AF: 0.00285

Gnomad4 SAS exome AF: 0.0398

Gnomad4 FIN exome AF: 0.0857

Gnomad4 NFE exome AF: 0.111

Gnomad4 OTH exome AF: 0.107

GnomAD4 genome AF: 0.162 AC: 24602 AN: 152162 Hom.: 2852 Cov.: 33 AF XY: 0.157 AC XY: 11706 AN XY: 74392

Gnomad4 AFR AF: 0.328

Gnomad4 AMR AF: 0.0989

Gnomad4 ASJ AF: 0.103

Gnomad4 EAS AF: 0.00426

Gnomad4 SAS AF: 0.0350

Gnomad4 FIN AF: 0.0789

Gnomad4 NFE AF: 0.114

Gnomad4 OTH AF: 0.131

Alfa AF: 0.140 Hom.: 913

Bravo AF: 0.170

Asia WGS AF: 0.0510 AC: 179 AN: 3478

EpiCase AF: 0.106

EpiControl AF: 0.106

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 29, 2024	- -
Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Nov 27, 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	-0.83
Cadd	Benign	2.1
Dann	Benign	0.30

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000014
dbscSNV1_RF	Benign	0.0
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

Other links and lift over

dbSNP: rs7142689; hg19: chr14-65236453;