11-66685507-G-A

Variant names:

• chr11-66685507-G-A
• rs11828658
• NM_006946.4:c.*364C>T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_006946.4(SPTBN2):​c.*364C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00611 in 313,170 control chromosomes in the GnomAD database, including 48 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.011 (41 hom., cov: 31)
  • Exomes 𝑓: 0.0015 (7 hom.)
• Consequence: SPTBN2 NM_006946.4 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.965

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 11-66685507-G-A is Benign according to our data. Variant chr11-66685507-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 305518.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.011 (1671/152196) while in subpopulation AFR AF= 0.0376 (1560/41508). AF 95% confidence interval is 0.036. There are 41 homozygotes in gnomad4. There are 787 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 41 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPTBN2	NM_006946.4	c.*364C>T		3_prime_UTR_variant	Exon 38 of 38	ENST00000533211.6	NP_008877.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPTBN2	ENST00000533211	c.*364C>T		3_prime_UTR_variant	Exon 38 of 38	5	NM_006946.4	ENSP00000432568.1
SPTBN2	ENST00000529997	c.*732C>T		3_prime_UTR_variant	Exon 35 of 35	5		ENSP00000433593.1
SPTBN2	ENST00000647510.2	n.*216+148C>T		intron_variant	Intron 38 of 38			ENSP00000508362.1

Frequencies

GnomAD3 genomes AF: 0.0110 AC: 1668 AN: 152080 Hom.: 40 Cov.: 31

Gnomad AFR AF: 0.0376

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00524

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000220

Gnomad OTH AF: 0.00622

GnomAD4 exome AF: 0.00150 AC: 241 AN: 160974 Hom.: 7 Cov.: 0 AF XY: 0.00128 AC XY: 111 AN XY: 86668

Gnomad4 AFR exome AF: 0.0387

Gnomad4 AMR exome AF: 0.00381

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000136

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000753

Gnomad4 OTH exome AF: 0.00210

GnomAD4 genome AF: 0.0110 AC: 1671 AN: 152196 Hom.: 41 Cov.: 31 AF XY: 0.0106 AC XY: 787 AN XY: 74404

Gnomad4 AFR AF: 0.0376

Gnomad4 AMR AF: 0.00523

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000194

Gnomad4 SAS AF: 0.000415

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000221

Gnomad4 OTH AF: 0.00616

Alfa AF: 0.00168 Hom.: 1

Bravo AF: 0.0123

Asia WGS AF: 0.00231 AC: 8 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Autosomal dominant cerebellar ataxia Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.0
DANN	Benign	0.62

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: rs11828658; hg19: chr11-66452978;