rs17180252

chr14-64772598-G-A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001355436.2(SPTB):c.5535C>T(p.Leu1845=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0701 in 1,609,008 control chromosomes in the GnomAD database, including 4,415 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.056 (292 hom., cov: 33)
  • Exomes 𝑓: 0.072 (4123 hom.)
• Consequence: SPTB NM_001355436.2 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.0500

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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BP6: Variant 14-64772598-G-A is Benign according to our data. Variant chr14-64772598-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 257129.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-64772598-G-A is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=0.05 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0815 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SPTB	NM_001355436.2	c.5535C>T	p.Leu1845=	synonymous_variant	26/36	ENST00000644917.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SPTB	ENST00000644917.1	c.5535C>T	p.Leu1845=	synonymous_variant	26/36		NM_001355436.2	P1
SPTB	ENST00000553938.5	c.1530C>T	p.Leu510=	synonymous_variant	7/18	1
SPTB	ENST00000389722.7	c.5535C>T	p.Leu1845=	synonymous_variant	25/35	2		P1
SPTB	ENST00000389720.4	c.5535C>T	p.Leu1845=	synonymous_variant	26/32	5

Frequencies

GnomAD3 genomes AF: 0.0565 AC: 8602 AN: 152168 Hom.: 292 Cov.: 33

Gnomad AFR AF: 0.0172

Gnomad AMI AF: 0.0515

Gnomad AMR AF: 0.0529

Gnomad ASJ AF: 0.0550

Gnomad EAS AF: 0.0194

Gnomad SAS AF: 0.0290

Gnomad FIN AF: 0.0785

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0833

Gnomad OTH AF: 0.0435

GnomAD3 exomes AF: 0.0595 AC: 14583 AN: 245264 Hom.: 553 AF XY: 0.0599 AC XY: 7996 AN XY: 133440

Gnomad AFR exome AF: 0.0149

Gnomad AMR exome AF: 0.0410

Gnomad ASJ exome AF: 0.0508

Gnomad EAS exome AF: 0.0264

Gnomad SAS exome AF: 0.0307

Gnomad FIN exome AF: 0.0763

Gnomad NFE exome AF: 0.0828

Gnomad OTH exome AF: 0.0596

GnomAD4 exome AF: 0.0715 AC: 104186 AN: 1456722 Hom.: 4123 Cov.: 33 AF XY: 0.0708 AC XY: 51303 AN XY: 725100

Gnomad4 AFR exome AF: 0.0138

Gnomad4 AMR exome AF: 0.0438

Gnomad4 ASJ exome AF: 0.0518

Gnomad4 EAS exome AF: 0.0168

Gnomad4 SAS exome AF: 0.0308

Gnomad4 FIN exome AF: 0.0783

Gnomad4 NFE exome AF: 0.0802

Gnomad4 OTH exome AF: 0.0652

GnomAD4 genome AF: 0.0565 AC: 8603 AN: 152286 Hom.: 292 Cov.: 33 AF XY: 0.0565 AC XY: 4208 AN XY: 74468

Gnomad4 AFR AF: 0.0172

Gnomad4 AMR AF: 0.0529

Gnomad4 ASJ AF: 0.0550

Gnomad4 EAS AF: 0.0195

Gnomad4 SAS AF: 0.0288

Gnomad4 FIN AF: 0.0785

Gnomad4 NFE AF: 0.0833

Gnomad4 OTH AF: 0.0440

Alfa AF: 0.0753 Hom.: 187

Bravo AF: 0.0522

Asia WGS AF: 0.0560 AC: 194 AN: 3478

EpiCase AF: 0.0749

EpiControl AF: 0.0748

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 22, 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	-0.70
Cadd	Benign	12
Dann	Benign	0.93

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

Other links and lift over

dbSNP: rs17180252; hg19: chr14-65239316;