chr14-64774231-C-T

Position:

• chr14-64774231-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6 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. Variant has been reported in Lovd as Benign (no stars).

• 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

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 14-64774231-C-T is Benign according to our data. Variant chr14-64774231-C-T is described in Lovd as [Benign].
• 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/exons	MANE	Protein	UniProt
SPTB	NM_001355436.2	c.4973+166G>A		intron_variant		ENST00000644917.1	NP_001342365.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPTB	ENST00000644917.1	c.4973+166G>A		intron_variant			NM_001355436.2	ENSP00000495909	P1
SPTB	ENST00000553938.5	c.968+166G>A		intron_variant		1		ENSP00000451324
SPTB	ENST00000389720.4	c.4973+166G>A		intron_variant		5		ENSP00000374370
SPTB	ENST00000389722.7	c.4973+166G>A		intron_variant		2		ENSP00000374372	P1

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

Gnomad4 AFR AF: 0.422

Gnomad4 AMR AF: 0.193

Gnomad4 ASJ AF: 0.233

Gnomad4 EAS AF: 0.0849

Gnomad4 SAS AF: 0.250

Gnomad4 FIN AF: 0.219

Gnomad4 NFE AF: 0.218

Gnomad4 OTH AF: 0.242

Alfa AF: 0.236 Hom.: 1914

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

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: rs11158559; hg19: chr14-65240949;