rs229673

Variant names:

• chr14-64815226-A-G
• rs229673
• NM_001355436.2:c.148+7721T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 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=-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 rank	MANE	Protein	UniProt
SPTB	NM_001355436.2	c.148+7721T>C		intron_variant	Intron 2 of 35	ENST00000644917.1	NP_001342365.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPTB	ENST00000644917.1	c.148+7721T>C		intron_variant	Intron 2 of 35		NM_001355436.2	ENSP00000495909.1
SPTB	ENST00000389722.7	c.148+7721T>C		intron_variant	Intron 1 of 34	2		ENSP00000374372.3
SPTB	ENST00000389720.4	c.148+7721T>C		intron_variant	Intron 2 of 31	5		ENSP00000374370.4

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

African (AFR) AF: 0.585 AC: 24270 AN: 41486

American (AMR) AF: 0.289 AC: 4423 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.347 AC: 1204 AN: 3468

East Asian (EAS) AF: 0.353 AC: 1827 AN: 5178

South Asian (SAS) AF: 0.479 AC: 2309 AN: 4824

European-Finnish (FIN) AF: 0.263 AC: 2778 AN: 10580

Middle Eastern (MID) AF: 0.327 AC: 96 AN: 294

European-Non Finnish (NFE) AF: 0.272 AC: 18479 AN: 67978

Other (OTH) AF: 0.354 AC: 748 AN: 2114

Alfa AF: 0.307 Hom.: 4157

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
PhyloP100		-0.15
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: rs229673; hg19: chr14-65281944;