14-64836533-T-C

Variant names:

• chr14-64836533-T-C
• rs2649196
• NM_001355436.2:c.-51-13388A>G

Variant summary

Our verdict is Benign. The variant received -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
• 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=-0.88).
• 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 rank	MANE	Protein	UniProt
SPTB	NM_001355436.2	c.-51-13388A>G		intron_variant	Intron 1 of 35	ENST00000644917.1	NP_001342365.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPTB	ENST00000644917.1	c.-51-13388A>G		intron_variant	Intron 1 of 35		NM_001355436.2	ENSP00000495909.1
SPTB	ENST00000389720.4	c.-51-13388A>G		intron_variant	Intron 1 of 31	5		ENSP00000374370.4

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

African (AFR) AF: 0.639 AC: 26400 AN: 41312

American (AMR) AF: 0.268 AC: 4081 AN: 15214

Ashkenazi Jewish (ASJ) AF: 0.328 AC: 1134 AN: 3462

East Asian (EAS) AF: 0.169 AC: 872 AN: 5150

South Asian (SAS) AF: 0.386 AC: 1849 AN: 4794

European-Finnish (FIN) AF: 0.169 AC: 1769 AN: 10482

Middle Eastern (MID) AF: 0.344 AC: 101 AN: 294

European-Non Finnish (NFE) AF: 0.245 AC: 16594 AN: 67862

Other (OTH) AF: 0.332 AC: 700 AN: 2106

Alfa AF: 0.282 Hom.: 3622

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
PhyloP100		0.26
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: rs2649196; hg19: chr14-65303251;