rs2941583

Positions:

• chr2-54641346-C-T

Variant summary

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

The ENST00000356805.9(SPTBN1):​c.3859-1637C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.78 in 152,196 control chromosomes in the GnomAD database, including 47,107 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 0.78 (47107 hom., cov: 32)
• Consequence: SPTBN1 ENST00000356805.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.31

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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.921 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPTBN1	NM_003128.3	c.3859-1637C>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.3859-1637C>T		intron_variant		1	NM_003128.3	ENSP00000349259	P1
SPTBN1	ENST00000333896.5	c.3820-1637C>T		intron_variant		1		ENSP00000334156

Frequencies

GnomAD3 genomes AF: 0.780 AC: 118571 AN: 152076 Hom.: 47037 Cov.: 32

Gnomad AFR AF: 0.929

Gnomad AMI AF: 0.799

Gnomad AMR AF: 0.749

Gnomad ASJ AF: 0.707

Gnomad EAS AF: 0.556

Gnomad SAS AF: 0.701

Gnomad FIN AF: 0.789

Gnomad MID AF: 0.722

Gnomad NFE AF: 0.721

Gnomad OTH AF: 0.761

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

GnomAD4 genome AF: 0.780 AC: 118701 AN: 152196 Hom.: 47107 Cov.: 32 AF XY: 0.779 AC XY: 57938 AN XY: 74404

Gnomad4 AFR AF: 0.929

Gnomad4 AMR AF: 0.749

Gnomad4 ASJ AF: 0.707

Gnomad4 EAS AF: 0.557

Gnomad4 SAS AF: 0.701

Gnomad4 FIN AF: 0.789

Gnomad4 NFE AF: 0.721

Gnomad4 OTH AF: 0.760

Alfa AF: 0.724 Hom.: 39670

Bravo AF: 0.781

Asia WGS AF: 0.673 AC: 2338 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.24
DANN	Benign	0.77
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs2941583; hg19: chr2-54868483;