rs12475342

Variant names:

• chr2-54655541-G-A
• rs12475342
• NM_003128.3:c.5961+333G>A

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 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=-0.81).
• 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 rank	MANE	Protein	UniProt
SPTBN1	NM_003128.3	c.5961+333G>A		intron_variant	Intron 28 of 35	ENST00000356805.9	NP_003119.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPTBN1	ENST00000356805.9	c.5961+333G>A		intron_variant	Intron 28 of 35	1	NM_003128.3	ENSP00000349259.4
SPTBN1	ENST00000333896.5	c.5922+333G>A		intron_variant	Intron 27 of 30	1		ENSP00000334156.5
SPTBN1	ENST00000496323.1	n.1475+333G>A		intron_variant	Intron 2 of 5	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

African (AFR) AF: 0.0885 AC: 3678 AN: 41558

American (AMR) AF: 0.355 AC: 5435 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.274 AC: 951 AN: 3468

East Asian (EAS) AF: 0.307 AC: 1588 AN: 5172

South Asian (SAS) AF: 0.322 AC: 1549 AN: 4818

European-Finnish (FIN) AF: 0.507 AC: 5356 AN: 10562

Middle Eastern (MID) AF: 0.192 AC: 56 AN: 292

European-Non Finnish (NFE) AF: 0.345 AC: 23470 AN: 67982

Other (OTH) AF: 0.289 AC: 611 AN: 2112

Alfa AF: 0.304 Hom.: 1007

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
PhyloP100		-0.039
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: rs12475342; hg19: chr2-54882678;