Genetic Variant TOP6BL:c.-109_-104dupCGGCGG (chr11-66744819-G-GGGCGGC) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_001302084.2(TOP6BL):c.-109_-104dupCGGCGG variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.121 in 1,221,768 control chromosomes in the GnomAD database, including 6,888 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.11 ( 1409 hom., cov: 0)

Exomes 𝑓: 0.12 ( 5479 hom. )

Consequence

TOP6BL
NM_001302084.2 5_prime_UTR

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.00

Variant links:

Genes affected

TOP6BL (HGNC:26197): (TOP6B like initiator of meiotic double strand breaks) Predicted to be involved in meiotic DNA double-strand break formation and reciprocal meiotic recombination. Predicted to be located in chromosome. Implicated in gestational trophoblastic neoplasm. [provided by Alliance of Genome Resources, Apr 2022]

TOP6BL links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.257 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
TOP6BL	NM_001302084.2 link	c.-109_-104dupCGGCGG	5_prime_UTR_variant	Exon 1 of 15	ENST00000540737.7	NP_001289013.1	Q8N6T0B4DXL1
TOP6BL	NM_024650.4 link	c.-50_-45dupCGGCGG	5_prime_UTR_variant	Exon 1 of 17		NP_078926.4	Q8N6T0-4
SPTBN2	XM_047427495.1 link	c.-489_-484dupGCCGCC	upstream_gene_variant			XP_047283451.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C11orf80	ENST00000540737 link	c.-109_-104dupCGGCGG		5_prime_UTR_variant	Exon 1 of 15	2	NM_001302084.2	ENSP00000444319.1		B4DXL1

Frequencies

GnomAD3 genomes

AF:

0.115

AC:

17005

AN:

148098

Hom.:

1406

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0496

Gnomad AMI

AF:

0.0919

Gnomad AMR

AF:

0.264

Gnomad ASJ

AF:

0.0926

Gnomad EAS

AF:

0.0224

Gnomad SAS

AF:

0.0762

Gnomad FIN

AF:

0.172

Gnomad MID

AF:

0.0452

Gnomad NFE

AF:

0.124

Gnomad OTH

AF:

0.110

GnomAD3 exomes

AF:

0.0936

AC:

1411

AN:

15072

Hom.:

126

AF XY:

0.0883

AC XY:

807

AN XY:

9136

show subpopulations

Gnomad AFR exome

AF:

0.0325

Gnomad AMR exome

AF:

0.248

Gnomad ASJ exome

AF:

0.0417

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0528

Gnomad FIN exome

AF:

0.138

Gnomad NFE exome

AF:

0.0831

Gnomad OTH exome

AF:

0.0750

GnomAD4 exome

AF:

0.122

AC:

130555

AN:

1073568

Hom.:

5479

Cov.:

AF XY:

0.121

AC XY:

62940

AN XY:

519386

show subpopulations

Gnomad4 AFR exome

AF:

0.0442

Gnomad4 AMR exome

AF:

0.357

Gnomad4 ASJ exome

AF:

0.0902

Gnomad4 EAS exome

AF:

0.0357

Gnomad4 SAS exome

AF:

0.0896

Gnomad4 FIN exome

AF:

0.184

Gnomad4 NFE exome

AF:

0.124

Gnomad4 OTH exome

AF:

0.113

GnomAD4 genome

AF:

0.115

AC:

17019

AN:

148200

Hom.:

1409

Cov.:

AF XY:

0.118

AC XY:

8527

AN XY:

72194

show subpopulations

Gnomad4 AFR

AF:

0.0496

Gnomad4 AMR

AF:

0.264

Gnomad4 ASJ

AF:

0.0926

Gnomad4 EAS

AF:

0.0224

Gnomad4 SAS

AF:

0.0769

Gnomad4 FIN

AF:

0.172

Gnomad4 NFE

AF:

0.124

Gnomad4 OTH

AF:

0.109

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over