14-64774231-C-T

Variant names:

• chr14-64774231-C-T
• rs11158559
• NM_001355436.2:c.4973+166G>A

Variant summary

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

The NM_001355436.2(SPTB):​c.4973+166G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.268 in 152,086 control chromosomes in the GnomAD database, including 6,223 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 0.27 (6223 hom., cov: 33)
• Consequence: SPTB NM_001355436.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.291
• Publications: 4 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 = 0.416 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPTB	NM_001355436.2	c.4973+166G>A		intron_variant	Intron 24 of 35	ENST00000644917.1	NP_001342365.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPTB	ENST00000644917.1	c.4973+166G>A		intron_variant	Intron 24 of 35		NM_001355436.2	ENSP00000495909.1
SPTB	ENST00000553938.5	c.968+166G>A		intron_variant	Intron 5 of 17	1		ENSP00000451324.1
SPTB	ENST00000389722.7	c.4973+166G>A		intron_variant	Intron 23 of 34	2		ENSP00000374372.3
SPTB	ENST00000389720.4	c.4973+166G>A		intron_variant	Intron 24 of 31	5		ENSP00000374370.4

Frequencies

GnomAD3 genomes AF: 0.268 AC: 40753 AN: 151968 Hom.: 6204 Cov.: 33

Gnomad AFR AF: 0.421

Gnomad AMI AF: 0.237

Gnomad AMR AF: 0.193

Gnomad ASJ AF: 0.233

Gnomad EAS AF: 0.0849

Gnomad SAS AF: 0.252

Gnomad FIN AF: 0.219

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.218

Gnomad OTH AF: 0.243

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

GnomAD4 genome AF: 0.268 AC: 40809 AN: 152086 Hom.: 6223 Cov.: 33 AF XY: 0.267 AC XY: 19882 AN XY: 74342

African (AFR) AF: 0.422 AC: 17469 AN: 41438

American (AMR) AF: 0.193 AC: 2949 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.233 AC: 808 AN: 3470

East Asian (EAS) AF: 0.0849 AC: 440 AN: 5184

South Asian (SAS) AF: 0.250 AC: 1206 AN: 4816

European-Finnish (FIN) AF: 0.219 AC: 2318 AN: 10588

Middle Eastern (MID) AF: 0.265 AC: 78 AN: 294

European-Non Finnish (NFE) AF: 0.218 AC: 14813 AN: 67966

Other (OTH) AF: 0.242 AC: 512 AN: 2114

Alfa AF: 0.259 Hom.: 5163

Bravo AF: 0.273

Asia WGS AF: 0.223 AC: 777 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	4.8
DANN	Benign	0.60
PhyloP100		-0.29
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: rs11158559; hg19: chr14-65240949;