11-66843174-G-C

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_001302084.2(C11orf80):c.1476G>C(p.Val492=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.248 in 1,610,532 control chromosomes in the GnomAD database, including 51,072 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.24 (4431 hom., cov: 33)
  • Exomes 𝑓: 0.25 (46641 hom.)
• Consequence: C11orf80 NM_001302084.2 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.379

Genes affected

C11orf80 (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]

RCE1 (HGNC:13721): (Ras converting CAAX endopeptidase 1) This gene encodes an integral membrane protein which is classified as a member of the metalloproteinase family. This enzyme is thought to function in the maintenance and processing of CAAX-type prenylated proteins. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).
• BP6: Variant 11-66843174-G-C is Benign according to our data. Variant chr11-66843174-G-C is described in ClinVar as [Benign]. Clinvar id is 3060507.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.379 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.255 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
C11orf80	NM_001302084.2	c.1476G>C	p.Val492=	synonymous_variant	15/15	ENST00000540737.7
C11orf80	NM_024650.3	c.1974G>C	p.Val658=	synonymous_variant	17/17

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
C11orf80	ENST00000540737.7	c.1476G>C	p.Val492=	synonymous_variant	15/15	2	NM_001302084.2	A2

Frequencies

GnomAD3 genomes AF: 0.240 AC: 36485 AN: 152072 Hom.: 4434 Cov.: 33

Gnomad AFR AF: 0.228

Gnomad AMI AF: 0.197

Gnomad AMR AF: 0.210

Gnomad ASJ AF: 0.313

Gnomad EAS AF: 0.160

Gnomad SAS AF: 0.140

Gnomad FIN AF: 0.267

Gnomad MID AF: 0.320

Gnomad NFE AF: 0.259

Gnomad OTH AF: 0.255

GnomAD3 exomes AF: 0.223 AC: 53666 AN: 241070 Hom.: 6403 AF XY: 0.225 AC XY: 29731 AN XY: 132040

Gnomad AFR exome AF: 0.222

Gnomad AMR exome AF: 0.145

Gnomad ASJ exome AF: 0.314

Gnomad EAS exome AF: 0.171

Gnomad SAS exome AF: 0.130

Gnomad FIN exome AF: 0.272

Gnomad NFE exome AF: 0.263

Gnomad OTH exome AF: 0.243

GnomAD4 exome AF: 0.249 AC: 363098 AN: 1458342 Hom.: 46641 Cov.: 36 AF XY: 0.247 AC XY: 179189 AN XY: 725340

Gnomad4 AFR exome AF: 0.225

Gnomad4 AMR exome AF: 0.152

Gnomad4 ASJ exome AF: 0.306

Gnomad4 EAS exome AF: 0.154

Gnomad4 SAS exome AF: 0.133

Gnomad4 FIN exome AF: 0.269

Gnomad4 NFE exome AF: 0.264

Gnomad4 OTH exome AF: 0.247

GnomAD4 genome AF: 0.240 AC: 36483 AN: 152190 Hom.: 4431 Cov.: 33 AF XY: 0.238 AC XY: 17726 AN XY: 74404

Gnomad4 AFR AF: 0.228

Gnomad4 AMR AF: 0.210

Gnomad4 ASJ AF: 0.313

Gnomad4 EAS AF: 0.160

Gnomad4 SAS AF: 0.140

Gnomad4 FIN AF: 0.267

Gnomad4 NFE AF: 0.259

Gnomad4 OTH AF: 0.256

Alfa AF: 0.262 Hom.: 1708

Bravo AF: 0.237

Asia WGS AF: 0.155 AC: 541 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

TOP6BL-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 21, 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

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
Cadd	Benign	5.5
Dann	Benign	0.59

Splicing

Name	Calibrated prediction	Score	Prediction
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

Publications

LitVar

Other links and lift over

dbSNP: rs7570; hg19: chr11-66610645; COSMIC: COSV58992483; COSMIC: COSV58992483;