rs17046067

Positions:

• chr2-54640359-C-T

Variant summary

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

The NM_003128.3(SPTBN1):​c.3858+2556C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.149 in 151,986 control chromosomes in the GnomAD database, including 1,784 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 0.15 (1784 hom., cov: 32)
• Consequence: SPTBN1 NM_003128.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.170

Genes affected

SPTBN1 (HGNC:11275): (spectrin beta, non-erythrocytic 1) Spectrin is an actin crosslinking and molecular scaffold protein that links the plasma membrane to the actin cytoskeleton, and functions in the determination of cell shape, arrangement of transmembrane proteins, and organization of organelles. It is composed of two antiparallel dimers of alpha- and beta- subunits. This gene is one member of a family of beta-spectrin genes. The encoded protein contains an N-terminal actin-binding domain, and 17 spectrin repeats which are involved in dimer formation. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.181 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPTBN1	NM_003128.3	c.3858+2556C>T		intron_variant		ENST00000356805.9	NP_003119.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPTBN1	ENST00000356805.9	c.3858+2556C>T		intron_variant		1	NM_003128.3	ENSP00000349259	P1
SPTBN1	ENST00000333896.5	c.3819+2556C>T		intron_variant		1		ENSP00000334156

Frequencies

GnomAD3 genomes AF: 0.149 AC: 22656 AN: 151868 Hom.: 1785 Cov.: 32

Gnomad AFR AF: 0.131

Gnomad AMI AF: 0.180

Gnomad AMR AF: 0.109

Gnomad ASJ AF: 0.131

Gnomad EAS AF: 0.0932

Gnomad SAS AF: 0.0832

Gnomad FIN AF: 0.118

Gnomad MID AF: 0.204

Gnomad NFE AF: 0.184

Gnomad OTH AF: 0.140

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

GnomAD4 genome AF: 0.149 AC: 22657 AN: 151986 Hom.: 1784 Cov.: 32 AF XY: 0.144 AC XY: 10666 AN XY: 74312

Gnomad4 AFR AF: 0.130

Gnomad4 AMR AF: 0.109

Gnomad4 ASJ AF: 0.131

Gnomad4 EAS AF: 0.0930

Gnomad4 SAS AF: 0.0826

Gnomad4 FIN AF: 0.118

Gnomad4 NFE AF: 0.184

Gnomad4 OTH AF: 0.140

Alfa AF: 0.165 Hom.: 288

Bravo AF: 0.148

Asia WGS AF: 0.105 AC: 368 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	5.0
DANN	Benign	0.55

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: rs17046067; hg19: chr2-54867496;