rs151122248

Positions:

• chr11-66705671-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_006946.4(SPTBN2):​c.1807+13C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00179 in 1,610,056 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0013 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0019 (7 hom.)
• Consequence: SPTBN2 NM_006946.4 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.466

Genes affected

SPTBN2 (HGNC:11276): (spectrin beta, non-erythrocytic 2) Spectrins are principle components of a cell's membrane-cytoskeleton and are composed of two alpha and two beta spectrin subunits. The protein encoded by this gene (SPTBN2), is called spectrin beta non-erythrocytic 2 or beta-III spectrin. It is related to, but distinct from, the beta-II spectrin gene which is also known as spectrin beta non-erythrocytic 1 (SPTBN1). SPTBN2 regulates the glutamate signaling pathway by stabilizing the glutamate transporter EAAT4 at the surface of the plasma membrane. Mutations in this gene cause a form of spinocerebellar ataxia, SCA5, that is characterized by neurodegeneration, progressive locomotor incoordination, dysarthria, and uncoordinated eye movements. [provided by RefSeq, Dec 2009]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 11-66705671-G-A is Benign according to our data. Variant chr11-66705671-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 305581.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00125 (191/152200) while in subpopulation NFE AF= 0.00199 (135/67996). AF 95% confidence interval is 0.00171. There are 0 homozygotes in gnomad4. There are 96 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAdExome4 at 7 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPTBN2	NM_006946.4	c.1807+13C>T		intron_variant		ENST00000533211.6	NP_008877.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPTBN2	ENST00000533211.6	c.1807+13C>T		intron_variant		5	NM_006946.4	ENSP00000432568	P1

Frequencies

GnomAD3 genomes AF: 0.00126 AC: 191 AN: 152082 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000459

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00311

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00199

Gnomad OTH AF: 0.000478

GnomAD3 exomes AF: 0.00156 AC: 377 AN: 242048 Hom.: 3 AF XY: 0.00148 AC XY: 196 AN XY: 132506

Gnomad AFR exome AF: 0.000531

Gnomad AMR exome AF: 0.000203

Gnomad ASJ exome AF: 0.000101

Gnomad EAS exome AF: 0.0000551

Gnomad SAS exome AF: 0.0000658

Gnomad FIN exome AF: 0.00386

Gnomad NFE exome AF: 0.00255

Gnomad OTH exome AF: 0.000994

GnomAD4 exome AF: 0.00185 AC: 2698 AN: 1457856 Hom.: 7 Cov.: 35 AF XY: 0.00184 AC XY: 1334 AN XY: 725430

Gnomad4 AFR exome AF: 0.000329

Gnomad4 AMR exome AF: 0.000179

Gnomad4 ASJ exome AF: 0.000115

Gnomad4 EAS exome AF: 0.000151

Gnomad4 SAS exome AF: 0.000128

Gnomad4 FIN exome AF: 0.00329

Gnomad4 NFE exome AF: 0.00218

Gnomad4 OTH exome AF: 0.00123

GnomAD4 genome AF: 0.00125 AC: 191 AN: 152200 Hom.: 0 Cov.: 33 AF XY: 0.00129 AC XY: 96 AN XY: 74410

Gnomad4 AFR AF: 0.000457

Gnomad4 AMR AF: 0.0000654

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000208

Gnomad4 FIN AF: 0.00311

Gnomad4 NFE AF: 0.00199

Gnomad4 OTH AF: 0.000473

Alfa AF: 0.00169 Hom.: 1

Bravo AF: 0.00111

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Autosomal recessive spinocerebellar ataxia 14 Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Apr 27, 2017

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 11, 2023

- -

Autosomal dominant cerebellar ataxia Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	6.2
DANN	Benign	0.51

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs151122248; hg19: chr11-66473142;