Genetic Variant TOP6BL:c.-106_-104dupCGG (chr11-66744819-G-GGGC) – ACMG Classification: Benign (-9 pts)

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP6BA1

The NM_001302084.2(TOP6BL):c.-106_-104dupCGG variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.468 in 1,222,560 control chromosomes in the GnomAD database, including 109,539 homozygotes. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.44 ( 15707 hom., cov: 0)

Exomes 𝑓: 0.47 ( 93832 hom. )

Consequence

TOP6BL
NM_001302084.2 5_prime_UTR

Scores

Not classified

Clinical Significance

Benign no assertion criteria provided B:1

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 -9 ACMG points.

BP6

Variant 11-66744819-G-GGGC is Benign according to our data. Variant chr11-66744819-G-GGGC is described in ClinVar as [Benign]. Clinvar id is 3058840.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.603 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
TOP6BL	NM_001302084.2 link	c.-106_-104dupCGG	5_prime_UTR_variant	Exon 1 of 15	ENST00000540737.7	NP_001289013.1	Q8N6T0B4DXL1
TOP6BL	NM_024650.4 link	c.-47_-45dupCGG	5_prime_UTR_variant	Exon 1 of 17		NP_078926.4	Q8N6T0-4
SPTBN2	XM_047427495.1 link	c.-486_-484dupGCC	upstream_gene_variant			XP_047283451.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C11orf80	ENST00000540737 link	c.-106_-104dupCGG		5_prime_UTR_variant	Exon 1 of 15	2	NM_001302084.2	ENSP00000444319.1		B4DXL1

Frequencies

GnomAD3 genomes

AF:

0.444

AC:

65659

AN:

148046

Hom.:

15705

Cov.:

show subpopulations

Gnomad AFR

AF:

0.263

Gnomad AMI

AF:

0.602

Gnomad AMR

AF:

0.400

Gnomad ASJ

AF:

0.487

Gnomad EAS

AF:

0.413

Gnomad SAS

AF:

0.624

Gnomad FIN

AF:

0.521

Gnomad MID

AF:

0.516

Gnomad NFE

AF:

0.537

Gnomad OTH

AF:

0.457

GnomAD3 exomes

AF:

0.519

AC:

7822

AN:

15072

Hom.:

1763

AF XY:

0.534

AC XY:

4880

AN XY:

9136

show subpopulations

Gnomad AFR exome

AF:

0.179

Gnomad AMR exome

AF:

0.466

Gnomad ASJ exome

AF:

0.501

Gnomad EAS exome

AF:

0.378

Gnomad SAS exome

AF:

0.614

Gnomad FIN exome

AF:

0.473

Gnomad NFE exome

AF:

0.517

Gnomad OTH exome

AF:

0.510

GnomAD4 exome

AF:

0.471

AC:

506279

AN:

1074412

Hom.:

93832

Cov.:

AF XY:

0.473

AC XY:

245711

AN XY:

519658

show subpopulations

Gnomad4 AFR exome

AF:

0.232

Gnomad4 AMR exome

AF:

0.349

Gnomad4 ASJ exome

AF:

0.442

Gnomad4 EAS exome

AF:

0.388

Gnomad4 SAS exome

AF:

0.572

Gnomad4 FIN exome

AF:

0.464

Gnomad4 NFE exome

AF:

0.479

Gnomad4 OTH exome

AF:

0.455

GnomAD4 genome

AF:

0.443

AC:

65664

AN:

148148

Hom.:

15707

Cov.:

AF XY:

0.445

AC XY:

32097

AN XY:

72162

show subpopulations

Gnomad4 AFR

AF:

0.263

Gnomad4 AMR

AF:

0.401

Gnomad4 ASJ

AF:

0.487

Gnomad4 EAS

AF:

0.412

Gnomad4 SAS

AF:

0.622

Gnomad4 FIN

AF:

0.521

Gnomad4 NFE

AF:

0.537

Gnomad4 OTH

AF:

0.460

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

TOP6BL-related disorder

Benign:1

Nov 01, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over