rs116078747

Variant names:

• chr11-66707825-C-A
• rs116078747
• NM_006946.4:c.1351-7G>T

Your query was ambiguous. Multiple possible variants found:

• chr11-66707825-C-A
• chr11-66707825-C-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_006946.4(SPTBN2):​c.1351-7G>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00202 in 1,607,658 control chromosomes in the GnomAD database, including 72 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.011 (39 hom., cov: 33)
  • Exomes 𝑓: 0.0011 (33 hom.)
• Consequence: SPTBN2 NM_006946.4 splice_region, intron
• Scores: Splicing: ADA: 0.00002262
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -1.01
• Publications: 1 publications found

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]

SPTBN2 Gene-Disease associations (from GenCC):

• spinocerebellar ataxia type 5

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: PanelApp Australia, ClinGen, G2P, Orphanet, Labcorp Genetics (formerly Invitae), Illumina
• autosomal recessive spinocerebellar ataxia 14

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: PanelApp Australia, G2P, Orphanet, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 11-66707825-C-A is Benign according to our data. Variant chr11-66707825-C-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 305587.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0106 (1620/152272) while in subpopulation AFR AF = 0.0365 (1516/41554). AF 95% confidence interval is 0.035. There are 39 homozygotes in GnomAd4. There are 759 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 39 AD,AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006946.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPTBN2	NM_006946.4	MANE Select	c.1351-7G>T		splice_region intron	N/A	NP_008877.2	O15020-1
	SPTBN2	NM_001411025.1		c.1372-7G>T		splice_region intron	N/A	NP_001397954.1	A0A087WYQ1
	SPTBN2	NM_001437541.1		c.1351-7G>T		splice_region intron	N/A	NP_001424470.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPTBN2	ENST00000533211.6	TSL:5 MANE Select	c.1351-7G>T		splice_region intron	N/A	ENSP00000432568.1	O15020-1
	SPTBN2	ENST00000309996.7	TSL:1	c.1351-7G>T		splice_region intron	N/A	ENSP00000311489.2	O15020-1
	SPTBN2	ENST00000617502.5	TSL:5	c.1372-7G>T		splice_region intron	N/A	ENSP00000482000.2	A0A087WYQ1

Frequencies

GnomAD3 genomes AF: 0.0106 AC: 1617 AN: 152154 Hom.: 38 Cov.: 33

Gnomad AFR AF: 0.0365

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00504

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000176

Gnomad OTH AF: 0.00623

GnomAD2 exomes AF: 0.00298 AC: 724 AN: 243132 AF XY: 0.00223

Gnomad AFR exome AF: 0.0389

Gnomad AMR exome AF: 0.00226

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000137

Gnomad OTH exome AF: 0.00133

GnomAD4 exome AF: 0.00111 AC: 1622 AN: 1455386 Hom.: 33 Cov.: 32 AF XY: 0.000968 AC XY: 701 AN XY: 724180

African (AFR) AF: 0.0374 AC: 1253 AN: 33468

American (AMR) AF: 0.00257 AC: 115 AN: 44684

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26108

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.000116 AC: 10 AN: 86134

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47508

Middle Eastern (MID) AF: 0.00141 AC: 8 AN: 5692

European-Non Finnish (NFE) AF: 0.0000468 AC: 52 AN: 1111786

Other (OTH) AF: 0.00305 AC: 184 AN: 60312

GnomAD4 genome AF: 0.0106 AC: 1620 AN: 152272 Hom.: 39 Cov.: 33 AF XY: 0.0102 AC XY: 759 AN XY: 74466

African (AFR) AF: 0.0365 AC: 1516 AN: 41554

American (AMR) AF: 0.00503 AC: 77 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.000415 AC: 2 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000176 AC: 12 AN: 68012

Other (OTH) AF: 0.00616 AC: 13 AN: 2110

Alfa AF: 0.00342 Hom.: 2

Bravo AF: 0.0120

EpiCase AF: 0.000164

EpiControl AF: 0.000237

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	Autosomal recessive spinocerebellar ataxia 14 (1)
-	-	1	Spinocerebellar ataxia type 5 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.27
DANN	Benign	0.69
PhyloP100		-1.0
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000023
dbscSNV1_RF	Benign	0.0060
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: rs116078747; hg19: chr11-66475296;