NM_003128.3:c.5823-586T>C

Variant names:

• chr2-54654484-T-C
• rs2941584
• NM_003128.3:c.5823-586T>C

Variant summary

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

The NM_003128.3(SPTBN1):​c.5823-586T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.636 in 152,066 control chromosomes in the GnomAD database, including 31,424 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 0.64 (31424 hom., cov: 32)
• Consequence: SPTBN1 NM_003128.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.67
• Publications: 12 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: Labcorp Genetics (formerly Invitae), ClinGen, G2P

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.682 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPTBN1	NM_003128.3	MANE Select	c.5823-586T>C		intron	N/A	NP_003119.2
	SPTBN1	NM_178313.3		c.5784-586T>C		intron	N/A	NP_842565.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPTBN1	ENST00000356805.9	TSL:1 MANE Select	c.5823-586T>C		intron	N/A	ENSP00000349259.4
	SPTBN1	ENST00000333896.5	TSL:1	c.5784-586T>C		intron	N/A	ENSP00000334156.5
	SPTBN1	ENST00000496323.1	TSL:2	n.1337-586T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.636 AC: 96599 AN: 151948 Hom.: 31408 Cov.: 32

Gnomad AFR AF: 0.535

Gnomad AMI AF: 0.793

Gnomad AMR AF: 0.690

Gnomad ASJ AF: 0.534

Gnomad EAS AF: 0.439

Gnomad SAS AF: 0.570

Gnomad FIN AF: 0.768

Gnomad MID AF: 0.573

Gnomad NFE AF: 0.688

Gnomad OTH AF: 0.626

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

GnomAD4 genome AF: 0.636 AC: 96663 AN: 152066 Hom.: 31424 Cov.: 32 AF XY: 0.636 AC XY: 47301 AN XY: 74364

African (AFR) AF: 0.535 AC: 22163 AN: 41452

American (AMR) AF: 0.690 AC: 10556 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.534 AC: 1851 AN: 3468

East Asian (EAS) AF: 0.439 AC: 2271 AN: 5168

South Asian (SAS) AF: 0.570 AC: 2742 AN: 4814

European-Finnish (FIN) AF: 0.768 AC: 8116 AN: 10572

Middle Eastern (MID) AF: 0.585 AC: 172 AN: 294

European-Non Finnish (NFE) AF: 0.688 AC: 46759 AN: 67992

Other (OTH) AF: 0.622 AC: 1313 AN: 2110

Alfa AF: 0.662 Hom.: 56042

Bravo AF: 0.625

Asia WGS AF: 0.542 AC: 1885 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.17
DANN	Benign	0.51
PhyloP100		-2.7
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: rs2941584; hg19: chr2-54881621;