rs2285002

Positions:

• chr14-64816958-G-A

Variant summary

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

The NM_001355436.2(SPTB):​c.148+5989C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.331 in 152,058 control chromosomes in the GnomAD database, including 8,723 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 0.33 (8723 hom., cov: 32)
• Consequence: SPTB NM_001355436.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.594

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=-0.74).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.408 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPTB	NM_001355436.2	c.148+5989C>T		intron_variant		ENST00000644917.1	NP_001342365.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPTB	ENST00000644917.1	c.148+5989C>T		intron_variant			NM_001355436.2	ENSP00000495909.1
SPTB	ENST00000389722.7	c.148+5989C>T		intron_variant		2		ENSP00000374372.3
SPTB	ENST00000389720.4	c.148+5989C>T		intron_variant		5		ENSP00000374370.4

Frequencies

GnomAD3 genomes AF: 0.331 AC: 50302 AN: 151940 Hom.: 8717 Cov.: 32

Gnomad AFR AF: 0.413

Gnomad AMI AF: 0.336

Gnomad AMR AF: 0.369

Gnomad ASJ AF: 0.359

Gnomad EAS AF: 0.150

Gnomad SAS AF: 0.414

Gnomad FIN AF: 0.270

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.290

Gnomad OTH AF: 0.312

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

GnomAD4 genome AF: 0.331 AC: 50349 AN: 152058 Hom.: 8723 Cov.: 32 AF XY: 0.331 AC XY: 24642 AN XY: 74338

Gnomad4 AFR AF: 0.413

Gnomad4 AMR AF: 0.369

Gnomad4 ASJ AF: 0.359

Gnomad4 EAS AF: 0.150

Gnomad4 SAS AF: 0.412

Gnomad4 FIN AF: 0.270

Gnomad4 NFE AF: 0.290

Gnomad4 OTH AF: 0.310

Alfa AF: 0.311 Hom.: 3921

Bravo AF: 0.339

Asia WGS AF: 0.324 AC: 1127 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	1.3
DANN	Benign	0.66

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: rs2285002; hg19: chr14-65283676;