2-54457420-A-G

Position:

• chr2-54457420-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003128.3(SPTBN1):​c.-48+902A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.758 in 152,478 control chromosomes in the GnomAD database, including 45,046 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 0.76 (44952 hom., cov: 31)
  • Exomes 𝑓: 0.63 (94 hom.)
• Consequence: SPTBN1 NM_003128.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.855

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=-0.86).
• 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/exons	MANE	Protein	UniProt
SPTBN1	NM_003128.3	c.-48+902A>G		intron_variant		ENST00000356805.9	NP_003119.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPTBN1	ENST00000356805.9	c.-48+902A>G		intron_variant		1	NM_003128.3	ENSP00000349259	P1
SPTBN1	ENST00000389980.7	c.-48+113A>G		intron_variant		1		ENSP00000374630

Frequencies

GnomAD3 genomes AF: 0.759 AC: 115247 AN: 151904 Hom.: 44895 Cov.: 31

Gnomad AFR AF: 0.934

Gnomad AMI AF: 0.716

Gnomad AMR AF: 0.755

Gnomad ASJ AF: 0.651

Gnomad EAS AF: 0.875

Gnomad SAS AF: 0.801

Gnomad FIN AF: 0.763

Gnomad MID AF: 0.709

Gnomad NFE AF: 0.648

Gnomad OTH AF: 0.719

GnomAD4 exome AF: 0.625 AC: 285 AN: 456 Hom.: 94 AF XY: 0.592 AC XY: 167 AN XY: 282

Gnomad4 AFR exome AF: 1.00

Gnomad4 AMR exome AF: 0.875

Gnomad4 ASJ exome AF: 0.875

Gnomad4 EAS exome AF: 0.800

Gnomad4 FIN exome AF: 0.700

Gnomad4 NFE exome AF: 0.568

Gnomad4 OTH exome AF: 0.750

GnomAD4 genome AF: 0.759 AC: 115362 AN: 152022 Hom.: 44952 Cov.: 31 AF XY: 0.767 AC XY: 56966 AN XY: 74294

Gnomad4 AFR AF: 0.934

Gnomad4 AMR AF: 0.755

Gnomad4 ASJ AF: 0.651

Gnomad4 EAS AF: 0.875

Gnomad4 SAS AF: 0.800

Gnomad4 FIN AF: 0.763

Gnomad4 NFE AF: 0.648

Gnomad4 OTH AF: 0.719

Alfa AF: 0.664 Hom.: 58208

Bravo AF: 0.765

Asia WGS AF: 0.844 AC: 2934 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	10
DANN	Benign	0.54

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: rs11898505; hg19: chr2-54684557;