chr11-66744819-G-GGGC

Position:

• chr11-66744819-G-GGGC

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP6 BA1

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
• Clinical Significance: Benign no assertion criteria provided B:1
• 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]

C11orf80 (HGNC:):

ACMG classification

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	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TOP6BL	NM_001302084.2	c.-106_-104dupCGG		5_prime_UTR_variant	1/15	ENST00000540737.7	NP_001289013.1
TOP6BL	NM_024650.3	c.101_103dupCGG	p.Ala34dup	disruptive_inframe_insertion	1/17		NP_078926.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
C11orf80	ENST00000540737	c.-106_-104dupCGG		5_prime_UTR_variant	1/15	2	NM_001302084.2	ENSP00000444319.1

Frequencies

GnomAD3 genomes AF: 0.444 AC: 65659 AN: 148046 Hom.: 15705 Cov.: 0

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

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.: 31 AF XY: 0.473 AC XY: 245711 AN XY: 519658

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.: 0 AF XY: 0.445 AC XY: 32097 AN XY: 72162

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

Submissions by phenotype

TOP6BL-related disorder Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Nov 01, 2019

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

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;