rs6734445

Variant names:

• chr2-54570661-C-T
• rs6734445
• NM_003128.3:c.149-28431C>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.149-28431C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.262 in 152,072 control chromosomes in the GnomAD database, including 6,849 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 0.26 (6849 hom., cov: 32)
• Consequence: SPTBN1 NM_003128.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.52
• 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: 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=-0.79).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.49 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.149-28431C>T		intron	N/A	NP_003119.2
	SPTBN1	NM_178313.3		c.109+11774C>T		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.149-28431C>T		intron	N/A	ENSP00000349259.4
	SPTBN1	ENST00000333896.5	TSL:1	c.109+11774C>T		intron	N/A	ENSP00000334156.5
	SPTBN1	ENST00000389980.7	TSL:1	c.149-28431C>T		intron	N/A	ENSP00000374630.3

Frequencies

GnomAD3 genomes AF: 0.262 AC: 39780 AN: 151954 Hom.: 6834 Cov.: 32

Gnomad AFR AF: 0.496

Gnomad AMI AF: 0.180

Gnomad AMR AF: 0.164

Gnomad ASJ AF: 0.156

Gnomad EAS AF: 0.122

Gnomad SAS AF: 0.147

Gnomad FIN AF: 0.120

Gnomad MID AF: 0.304

Gnomad NFE AF: 0.189

Gnomad OTH AF: 0.238

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

GnomAD4 genome AF: 0.262 AC: 39831 AN: 152072 Hom.: 6849 Cov.: 32 AF XY: 0.254 AC XY: 18859 AN XY: 74354

African (AFR) AF: 0.496 AC: 20553 AN: 41432

American (AMR) AF: 0.163 AC: 2497 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.156 AC: 542 AN: 3470

East Asian (EAS) AF: 0.122 AC: 632 AN: 5178

South Asian (SAS) AF: 0.145 AC: 701 AN: 4822

European-Finnish (FIN) AF: 0.120 AC: 1273 AN: 10582

Middle Eastern (MID) AF: 0.303 AC: 89 AN: 294

European-Non Finnish (NFE) AF: 0.189 AC: 12882 AN: 67990

Other (OTH) AF: 0.236 AC: 498 AN: 2110

Alfa AF: 0.206 Hom.: 2145

Bravo AF: 0.275

Asia WGS AF: 0.170 AC: 594 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	1.0
DANN	Benign	0.61
PhyloP100		-1.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
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: rs6734445; hg19: chr2-54797798;