2-54662253-C-T

Variant names:

• chr2-54662253-C-T
• rs1047499
• ENST00000333896.5:c.*2167C>T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_178313.3(SPTBN1):​c.*2167C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.739 in 985,206 control chromosomes in the GnomAD database, including 270,713 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 0.79 (48655 hom., cov: 32)
  • Exomes 𝑓: 0.73 (222058 hom.)
• Consequence: SPTBN1 NM_178313.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.510

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-AS2 (HGNC:40563): (SPTBN1 antisense RNA 2)

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.38).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.926 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPTBN1	NM_003128.3	c.6421-2200C>T		intron_variant	Intron 32 of 35	ENST00000356805.9	NP_003119.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPTBN1	ENST00000356805.9	c.6421-2200C>T		intron_variant	Intron 32 of 35	1	NM_003128.3	ENSP00000349259.4

Frequencies

GnomAD3 genomes AF: 0.794 AC: 120685 AN: 152058 Hom.: 48593 Cov.: 32

Gnomad AFR AF: 0.933

Gnomad AMI AF: 0.799

Gnomad AMR AF: 0.765

Gnomad ASJ AF: 0.718

Gnomad EAS AF: 0.571

Gnomad SAS AF: 0.706

Gnomad FIN AF: 0.791

Gnomad MID AF: 0.728

Gnomad NFE AF: 0.743

Gnomad OTH AF: 0.784

GnomAD4 exome AF: 0.729 AC: 607462 AN: 833030 Hom.: 222058 Cov.: 39 AF XY: 0.730 AC XY: 280635 AN XY: 384686

Gnomad4 AFR exome AF: 0.955

Gnomad4 AMR exome AF: 0.739

Gnomad4 ASJ exome AF: 0.723

Gnomad4 EAS exome AF: 0.585

Gnomad4 SAS exome AF: 0.707

Gnomad4 FIN exome AF: 0.771

Gnomad4 NFE exome AF: 0.726

Gnomad4 OTH exome AF: 0.729

GnomAD4 genome AF: 0.794 AC: 120807 AN: 152176 Hom.: 48655 Cov.: 32 AF XY: 0.792 AC XY: 58932 AN XY: 74392

Gnomad4 AFR AF: 0.933

Gnomad4 AMR AF: 0.765

Gnomad4 ASJ AF: 0.718

Gnomad4 EAS AF: 0.572

Gnomad4 SAS AF: 0.706

Gnomad4 FIN AF: 0.791

Gnomad4 NFE AF: 0.743

Gnomad4 OTH AF: 0.783

Alfa AF: 0.745 Hom.: 32606

Bravo AF: 0.796

Asia WGS AF: 0.680 AC: 2368 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.38
CADD	Benign	15
DANN	Benign	0.76

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: rs1047499; hg19: chr2-54889390;