rs17046067

Variant names:

• chr2-54640359-C-T
• rs17046067
• NM_003128.3:c.3858+2556C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003128.3(SPTBN1):​c.3858+2556C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.149 in 151,986 control chromosomes in the GnomAD database, including 1,784 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 0.15 (1784 hom., cov: 32)
• Consequence: SPTBN1 NM_003128.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.170
• Publications: 4 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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.181 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPTBN1	NM_003128.3	c.3858+2556C>T		intron_variant	Intron 18 of 35	ENST00000356805.9	NP_003119.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPTBN1	ENST00000356805.9	c.3858+2556C>T		intron_variant	Intron 18 of 35	1	NM_003128.3	ENSP00000349259.4
SPTBN1	ENST00000333896.5	c.3819+2556C>T		intron_variant	Intron 17 of 30	1		ENSP00000334156.5

Frequencies

GnomAD3 genomes AF: 0.149 AC: 22656 AN: 151868 Hom.: 1785 Cov.: 32

Gnomad AFR AF: 0.131

Gnomad AMI AF: 0.180

Gnomad AMR AF: 0.109

Gnomad ASJ AF: 0.131

Gnomad EAS AF: 0.0932

Gnomad SAS AF: 0.0832

Gnomad FIN AF: 0.118

Gnomad MID AF: 0.204

Gnomad NFE AF: 0.184

Gnomad OTH AF: 0.140

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

GnomAD4 genome AF: 0.149 AC: 22657 AN: 151986 Hom.: 1784 Cov.: 32 AF XY: 0.144 AC XY: 10666 AN XY: 74312

African (AFR) AF: 0.130 AC: 5401 AN: 41412

American (AMR) AF: 0.109 AC: 1660 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.131 AC: 454 AN: 3462

East Asian (EAS) AF: 0.0930 AC: 481 AN: 5172

South Asian (SAS) AF: 0.0826 AC: 398 AN: 4818

European-Finnish (FIN) AF: 0.118 AC: 1252 AN: 10574

Middle Eastern (MID) AF: 0.209 AC: 61 AN: 292

European-Non Finnish (NFE) AF: 0.184 AC: 12491 AN: 67948

Other (OTH) AF: 0.140 AC: 295 AN: 2114

Alfa AF: 0.164 Hom.: 295

Bravo AF: 0.148

Asia WGS AF: 0.105 AC: 368 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	5.0
DANN	Benign	0.55
PhyloP100		-0.17
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: rs17046067; hg19: chr2-54867496;