rs12475342

Positions:

• chr2-54655541-G-A
• chr2-54655541-G-C

Variant summary

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

The NM_003128.3(SPTBN1):​c.5961+333G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.283 in 152,166 control chromosomes in the GnomAD database, including 7,443 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 0.28 (7443 hom., cov: 32)
• Consequence: SPTBN1 NM_003128.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0390

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=-0.81).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.347 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SPTBN1	NM_003128.3	c.5961+333G>A		intron_variant		ENST00000356805.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SPTBN1	ENST00000356805.9	c.5961+333G>A		intron_variant		1	NM_003128.3	P1
SPTBN1	ENST00000333896.5	c.5922+333G>A		intron_variant		1
SPTBN1	ENST00000496323.1	n.1475+333G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.283 AC: 43045 AN: 152048 Hom.: 7441 Cov.: 32

Gnomad AFR AF: 0.0886

Gnomad AMI AF: 0.404

Gnomad AMR AF: 0.355

Gnomad ASJ AF: 0.274

Gnomad EAS AF: 0.306

Gnomad SAS AF: 0.321

Gnomad FIN AF: 0.507

Gnomad MID AF: 0.175

Gnomad NFE AF: 0.345

Gnomad OTH AF: 0.290

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

GnomAD4 genome AF: 0.283 AC: 43061 AN: 152166 Hom.: 7443 Cov.: 32 AF XY: 0.290 AC XY: 21599 AN XY: 74398

Gnomad4 AFR AF: 0.0885

Gnomad4 AMR AF: 0.355

Gnomad4 ASJ AF: 0.274

Gnomad4 EAS AF: 0.307

Gnomad4 SAS AF: 0.322

Gnomad4 FIN AF: 0.507

Gnomad4 NFE AF: 0.345

Gnomad4 OTH AF: 0.289

Alfa AF: 0.313 Hom.: 1005

Bravo AF: 0.264

Asia WGS AF: 0.318 AC: 1104 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	3.9
DANN	Benign	0.58

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: rs12475342; hg19: chr2-54882678;