rs229673

chr14-64815226-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001355436.2(SPTB):c.148+7721T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.371 in 152,118 control chromosomes in the GnomAD database, including 12,002 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.37 (12002 hom., cov: 33)
• Consequence: SPTB NM_001355436.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.153

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.07).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.579 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SPTB	NM_001355436.2	c.148+7721T>C		intron_variant		ENST00000644917.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SPTB	ENST00000644917.1	c.148+7721T>C		intron_variant			NM_001355436.2	P1
SPTB	ENST00000389720.4	c.148+7721T>C		intron_variant		5
SPTB	ENST00000389722.7	c.148+7721T>C		intron_variant		2		P1

Frequencies

GnomAD3 genomes AF: 0.371 AC: 56388 AN: 151998 Hom.: 11981 Cov.: 33

Gnomad AFR AF: 0.585

Gnomad AMI AF: 0.346

Gnomad AMR AF: 0.290

Gnomad ASJ AF: 0.347

Gnomad EAS AF: 0.353

Gnomad SAS AF: 0.481

Gnomad FIN AF: 0.263

Gnomad MID AF: 0.326

Gnomad NFE AF: 0.272

Gnomad OTH AF: 0.353

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.371 AC: 56449 AN: 152118 Hom.: 12002 Cov.: 33 AF XY: 0.371 AC XY: 27563 AN XY: 74374

Gnomad4 AFR AF: 0.585

Gnomad4 AMR AF: 0.289

Gnomad4 ASJ AF: 0.347

Gnomad4 EAS AF: 0.353

Gnomad4 SAS AF: 0.479

Gnomad4 FIN AF: 0.263

Gnomad4 NFE AF: 0.272

Gnomad4 OTH AF: 0.354

Alfa AF: 0.307 Hom.: 3719

Bravo AF: 0.378

Asia WGS AF: 0.435 AC: 1514 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
Cadd	Benign	0.32
Dann	Benign	0.26

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: rs229673; hg19: chr14-65281944;