chr14-64816958-G-A

Variant names:

• chr14-64816958-G-A
• rs2285002
• NM_001355436.2:c.148+5989C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000644917.1(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 ENST00000644917.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.594
• Publications: 7 publications found

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]

SPTB Gene-Disease associations (from GenCC):

• hereditary spherocytosis type 2

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• elliptocytosis 3

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• hereditary elliptocytosis

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• hereditary spherocytosis

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000644917.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPTB	NM_001355436.2	MANE Select	c.148+5989C>T		intron	N/A	NP_001342365.1
	SPTB	NM_001024858.4		c.148+5989C>T		intron	N/A	NP_001020029.1
	SPTB	NM_001355437.2		c.148+5989C>T		intron	N/A	NP_001342366.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPTB	ENST00000644917.1	MANE Select	c.148+5989C>T		intron	N/A	ENSP00000495909.1
	SPTB	ENST00000389722.7	TSL:2	c.148+5989C>T		intron	N/A	ENSP00000374372.3
	SPTB	ENST00000389720.4	TSL:5	c.148+5989C>T		intron	N/A	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

African (AFR) AF: 0.413 AC: 17129 AN: 41464

American (AMR) AF: 0.369 AC: 5637 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.359 AC: 1246 AN: 3470

East Asian (EAS) AF: 0.150 AC: 779 AN: 5182

South Asian (SAS) AF: 0.412 AC: 1987 AN: 4820

European-Finnish (FIN) AF: 0.270 AC: 2863 AN: 10594

Middle Eastern (MID) AF: 0.259 AC: 76 AN: 294

European-Non Finnish (NFE) AF: 0.290 AC: 19674 AN: 67956

Other (OTH) AF: 0.310 AC: 653 AN: 2106

Alfa AF: 0.312 Hom.: 4360

Bravo AF: 0.339

Asia WGS AF: 0.324 AC: 1127 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	1.3
DANN	Benign	0.66
PhyloP100		-0.59
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2285002; hg19: chr14-65283676;