14-64852643-G-A

Position:

• chr14-64852643-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001355436.2(SPTB):​c.-52+27149C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.436 in 151,994 control chromosomes in the GnomAD database, including 18,076 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 0.44 (18076 hom., cov: 31)
• Consequence: SPTB NM_001355436.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.654

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.592 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SPTB	NM_001355436.2	c.-52+27149C>T		intron_variant		ENST00000644917.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SPTB	ENST00000644917.1	c.-52+27149C>T		intron_variant			NM_001355436.2	P1
SPTB	ENST00000389720.4	c.-52+27149C>T		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.436 AC: 66257 AN: 151876 Hom.: 18074 Cov.: 31

Gnomad AFR AF: 0.111

Gnomad AMI AF: 0.562

Gnomad AMR AF: 0.556

Gnomad ASJ AF: 0.515

Gnomad EAS AF: 0.191

Gnomad SAS AF: 0.447

Gnomad FIN AF: 0.574

Gnomad MID AF: 0.434

Gnomad NFE AF: 0.597

Gnomad OTH AF: 0.453

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

GnomAD4 genome AF: 0.436 AC: 66261 AN: 151994 Hom.: 18076 Cov.: 31 AF XY: 0.435 AC XY: 32305 AN XY: 74272

Gnomad4 AFR AF: 0.111

Gnomad4 AMR AF: 0.557

Gnomad4 ASJ AF: 0.515

Gnomad4 EAS AF: 0.192

Gnomad4 SAS AF: 0.448

Gnomad4 FIN AF: 0.574

Gnomad4 NFE AF: 0.597

Gnomad4 OTH AF: 0.449

Alfa AF: 0.538 Hom.: 4846

Bravo AF: 0.415

Asia WGS AF: 0.315 AC: 1094 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	7.9
DANN	Benign	0.74

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: rs35955841; hg19: chr14-65319361;