rs11622977

chr14-64767290-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.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
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -1.62

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=-0.92).
• 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	UniProt
SPTB	NM_001355436.2	c.6269+13C>T		intron_variant		ENST00000644917.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SPTB	ENST00000644917.1	c.6269+13C>T		intron_variant			NM_001355436.2	P1

Frequencies

GnomAD3 genomes AF: 0.165 AC: 25018 AN: 152034 Hom.: 2921 Cov.: 33

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

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.: 33 AF XY: 0.106 AC XY: 77279 AN XY: 727006

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.: 33 AF XY: 0.160 AC XY: 11924 AN XY: 74396

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:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

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

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

Other links and lift over

dbSNP: rs11622977; hg19: chr14-65234008;