11-66744819-GGGCGGCGGCGGCGGC-GGGCGGCGGCGGCGGCGGCGGCGGC

Variant names:

• chr11-66744819-G-GGGCGGCGGC
• rs567536854
• NM_001302084.2:c.-112_-104dupCGGCGGCGG

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1 BS2

The NM_001302084.2(TOP6BL):​c.-112_-104dupCGGCGGCGG variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00881 in 1,227,660 control chromosomes in the GnomAD database, including 86 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.012 (21 hom., cov: 0)
  • Exomes 𝑓: 0.0084 (65 hom.)
• Consequence: TOP6BL NM_001302084.2 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00

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]

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 -8 ACMG points.

• BS1: Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.012 (1774/148276) while in subpopulation AMR AF= 0.0242 (364/15014). AF 95% confidence interval is 0.0222. There are 21 homozygotes in gnomad4. There are 911 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 21 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TOP6BL	NM_001302084.2	c.-112_-104dupCGGCGGCGG		5_prime_UTR_variant	Exon 1 of 15	ENST00000540737.7	NP_001289013.1
TOP6BL	NM_024650.4	c.-53_-45dupCGGCGGCGG		5_prime_UTR_variant	Exon 1 of 17		NP_078926.4
SPTBN2	XM_047427495.1	c.-492_-484dupGCCGCCGCC		upstream_gene_variant			XP_047283451.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C11orf80	ENST00000540737	c.-112_-104dupCGGCGGCGG		5_prime_UTR_variant	Exon 1 of 15	2	NM_001302084.2	ENSP00000444319.1

Frequencies

GnomAD3 genomes AF: 0.0120 AC: 1771 AN: 148174 Hom.: 21 Cov.: 0

Gnomad AFR AF: 0.0135

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0243

Gnomad ASJ AF: 0.00759

Gnomad EAS AF: 0.0146

Gnomad SAS AF: 0.00827

Gnomad FIN AF: 0.00742

Gnomad MID AF: 0.0129

Gnomad NFE AF: 0.00940

Gnomad OTH AF: 0.00932

GnomAD3 exomes AF: 0.00285 AC: 43 AN: 15072 Hom.: 0 AF XY: 0.00285 AC XY: 26 AN XY: 9136

Gnomad AFR exome AF: 0.00325

Gnomad AMR exome AF: 0.00420

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00279

Gnomad FIN exome AF: 0.000926

Gnomad NFE exome AF: 0.00387

Gnomad OTH exome AF: 0.00500

GnomAD4 exome AF: 0.00838 AC: 9041 AN: 1079384 Hom.: 65 Cov.: 31 AF XY: 0.00847 AC XY: 4421 AN XY: 522116

Gnomad4 AFR exome AF: 0.0123

Gnomad4 AMR exome AF: 0.0180

Gnomad4 ASJ exome AF: 0.00546

Gnomad4 EAS exome AF: 0.0134

Gnomad4 SAS exome AF: 0.00967

Gnomad4 FIN exome AF: 0.00457

Gnomad4 NFE exome AF: 0.00802

Gnomad4 OTH exome AF: 0.0100

GnomAD4 genome AF: 0.0120 AC: 1774 AN: 148276 Hom.: 21 Cov.: 0 AF XY: 0.0126 AC XY: 911 AN XY: 72240

Gnomad4 AFR AF: 0.0136

Gnomad4 AMR AF: 0.0242

Gnomad4 ASJ AF: 0.00759

Gnomad4 EAS AF: 0.0147

Gnomad4 SAS AF: 0.00829

Gnomad4 FIN AF: 0.00742

Gnomad4 NFE AF: 0.00940

Gnomad4 OTH AF: 0.00922

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs567536854; hg19: chr11-66512290;