2-54641346-C-T

Variant names:

• chr2-54641346-C-T
• rs2941583
• NM_003128.3:c.3859-1637C>T

Variant summary

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

The NM_003128.3(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 NM_003128.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.31
• Publications: 8 publications found

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]

SPTBN1 Gene-Disease associations (from GenCC):

• developmental delay, impaired speech, and behavioral abnormalities

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), G2P, PanelApp Australia

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003128.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPTBN1	NM_003128.3	MANE Select	c.3859-1637C>T		intron	N/A	NP_003119.2	Q01082-1
	SPTBN1	NM_178313.3		c.3820-1637C>T		intron	N/A	NP_842565.2	Q01082-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPTBN1	ENST00000356805.9	TSL:1 MANE Select	c.3859-1637C>T		intron	N/A	ENSP00000349259.4	Q01082-1
	SPTBN1	ENST00000333896.5	TSL:1	c.3820-1637C>T		intron	N/A	ENSP00000334156.5	Q01082-3
	SPTBN1	ENST00000898760.1		c.3859-1637C>T		intron	N/A	ENSP00000568819.1

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

African (AFR) AF: 0.929 AC: 38594 AN: 41538

American (AMR) AF: 0.749 AC: 11448 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.707 AC: 2453 AN: 3472

East Asian (EAS) AF: 0.557 AC: 2888 AN: 5182

South Asian (SAS) AF: 0.701 AC: 3381 AN: 4826

European-Finnish (FIN) AF: 0.789 AC: 8348 AN: 10584

Middle Eastern (MID) AF: 0.728 AC: 214 AN: 294

European-Non Finnish (NFE) AF: 0.721 AC: 49039 AN: 67994

Other (OTH) AF: 0.760 AC: 1609 AN: 2116

Alfa AF: 0.734 Hom.: 53273

Bravo AF: 0.781

Asia WGS AF: 0.673 AC: 2338 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.24
DANN	Benign	0.77
PhyloP100		-1.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs2941583; hg19: chr2-54868483;