2-54580520-T-C

Variant names:

• chr2-54580520-T-C
• rs3287
• NM_003128.3:c.149-18572T>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.149-18572T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.339 in 151,782 control chromosomes in the GnomAD database, including 11,200 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 0.34 (11200 hom., cov: 31)
• Consequence: SPTBN1 NM_003128.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.735
• Publications: 13 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.622 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPTBN1	NM_003128.3	c.149-18572T>C		intron_variant	Intron 2 of 35	ENST00000356805.9	NP_003119.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPTBN1	ENST00000356805.9	c.149-18572T>C		intron_variant	Intron 2 of 35	1	NM_003128.3	ENSP00000349259.4
SPTBN1	ENST00000333896.5	c.110-18572T>C		intron_variant	Intron 1 of 30	1		ENSP00000334156.5
SPTBN1	ENST00000389980.7	c.149-18572T>C		intron_variant	Intron 2 of 13	1		ENSP00000374630.3

Frequencies

GnomAD3 genomes AF: 0.339 AC: 51351 AN: 151664 Hom.: 11160 Cov.: 31

Gnomad AFR AF: 0.628

Gnomad AMI AF: 0.240

Gnomad AMR AF: 0.276

Gnomad ASJ AF: 0.189

Gnomad EAS AF: 0.127

Gnomad SAS AF: 0.209

Gnomad FIN AF: 0.168

Gnomad MID AF: 0.338

Gnomad NFE AF: 0.239

Gnomad OTH AF: 0.307

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

GnomAD4 genome AF: 0.339 AC: 51437 AN: 151782 Hom.: 11200 Cov.: 31 AF XY: 0.331 AC XY: 24560 AN XY: 74198

African (AFR) AF: 0.628 AC: 25945 AN: 41288

American (AMR) AF: 0.276 AC: 4207 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.189 AC: 655 AN: 3470

East Asian (EAS) AF: 0.126 AC: 654 AN: 5172

South Asian (SAS) AF: 0.208 AC: 1003 AN: 4818

European-Finnish (FIN) AF: 0.168 AC: 1769 AN: 10524

Middle Eastern (MID) AF: 0.342 AC: 100 AN: 292

European-Non Finnish (NFE) AF: 0.239 AC: 16247 AN: 67950

Other (OTH) AF: 0.304 AC: 640 AN: 2102

Alfa AF: 0.199 Hom.: 653

Bravo AF: 0.359

Asia WGS AF: 0.225 AC: 784 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	4.8
DANN	Benign	0.51
PhyloP100		0.73
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: rs3287; hg19: chr2-54807657;