rs2649196

chr14-64836533-T-Cchr14-64836533-T-G

Variant summary

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

The NM_001355436.2(SPTB):c.-51-13388A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.355 in 151,584 control chromosomes in the GnomAD database, including 12,070 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 0.35 (12070 hom., cov: 31)
• Consequence: SPTB NM_001355436.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.259

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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.633 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SPTB	NM_001355436.2	c.-51-13388A>G		intron_variant		ENST00000644917.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SPTB	ENST00000644917.1	c.-51-13388A>G		intron_variant			NM_001355436.2	P1
SPTB	ENST00000389720.4	c.-51-13388A>G		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.354 AC: 53663 AN: 151466 Hom.: 12023 Cov.: 31

Gnomad AFR AF: 0.639

Gnomad AMI AF: 0.291

Gnomad AMR AF: 0.269

Gnomad ASJ AF: 0.328

Gnomad EAS AF: 0.169

Gnomad SAS AF: 0.387

Gnomad FIN AF: 0.169

Gnomad MID AF: 0.342

Gnomad NFE AF: 0.245

Gnomad OTH AF: 0.328

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

GnomAD4 genome AF: 0.355 AC: 53764 AN: 151584 Hom.: 12070 Cov.: 31 AF XY: 0.350 AC XY: 25940 AN XY: 74050

Gnomad4 AFR AF: 0.639

Gnomad4 AMR AF: 0.268

Gnomad4 ASJ AF: 0.328

Gnomad4 EAS AF: 0.169

Gnomad4 SAS AF: 0.386

Gnomad4 FIN AF: 0.169

Gnomad4 NFE AF: 0.245

Gnomad4 OTH AF: 0.332

Alfa AF: 0.280 Hom.: 3167

Bravo AF: 0.372

Asia WGS AF: 0.347 AC: 1208 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	4.0
Dann	Benign	0.67

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: rs2649196; hg19: chr14-65303251;