rs6734445

Variant names:

• chr2-54570661-C-T
• rs6734445
• NM_003128.3:c.149-28431C>T

Variant summary

Our verdict is Benign. Variant got -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

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=-0.79).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.49 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPTBN1	NM_003128.3	c.149-28431C>T		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.149-28431C>T		intron_variant	Intron 2 of 35	1	NM_003128.3	ENSP00000349259.4
SPTBN1	ENST00000333896.5	c.109+11774C>T		intron_variant	Intron 1 of 30	1		ENSP00000334156.5
SPTBN1	ENST00000389980.7	c.149-28431C>T		intron_variant	Intron 2 of 13	1		ENSP00000374630.3
SPTBN1	ENST00000615901.4	c.149-28431C>T		intron_variant	Intron 2 of 37	5

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

Gnomad4 AFR AF: 0.496

Gnomad4 AMR AF: 0.163

Gnomad4 ASJ AF: 0.156

Gnomad4 EAS AF: 0.122

Gnomad4 SAS AF: 0.145

Gnomad4 FIN AF: 0.120

Gnomad4 NFE AF: 0.189

Gnomad4 OTH AF: 0.236

Alfa AF: 0.204 Hom.: 1886

Bravo AF: 0.275

Asia WGS AF: 0.170 AC: 594 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	1.0
DANN	Benign	0.61
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs6734445; hg19: chr2-54797798;