Variant 11-66788262-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_001302084.2(C11orf80):c.128T>C(p.Ile43Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00172 in 1,607,744 control chromosomes in the GnomAD database, including 43 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.0090 ( 23 hom., cov: 32)

Exomes 𝑓: 0.00096 ( 20 hom. )

Consequence

C11orf80
NM_001302084.2 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -2.10

Variant links:

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]

C11orf80 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0034433305).

BP6

Variant 11-66788262-T-C is Benign according to our data. Variant chr11-66788262-T-C is described in ClinVar as [Benign]. Clinvar id is 3050115.Status of the report is no_assertion_criteria_provided, 0 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00902 (1374/152348) while in subpopulation AFR AF= 0.0306 (1273/41586). AF 95% confidence interval is 0.0292. There are 23 homozygotes in gnomad4. There are 626 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 23 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
C11orf80	NM_001302084.2 linkuse as main transcript	c.128T>C	p.Ile43Thr	missense_variant	3/15	ENST00000540737.7	NP_001289013.1
C11orf80	NM_024650.3 linkuse as main transcript	c.626T>C	p.Ile209Thr	missense_variant	5/17		NP_078926.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
C11orf80	ENST00000540737.7 linkuse as main transcript	c.128T>C	p.Ile43Thr	missense_variant	3/15	2	NM_001302084.2	ENSP00000444319	A2

Frequencies

GnomAD3 genomes

AF:

0.00901

AC:

1371

AN:

152230

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0306

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00491

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000132

Gnomad OTH

AF:

0.00813

GnomAD3 exomes

AF:

0.00243

AC:

602

AN:

248168

Hom.:

AF XY:

0.00166

AC XY:

223

AN XY:

134570

show subpopulations

Gnomad AFR exome

AF:

0.0328

Gnomad AMR exome

AF:

0.00213

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000661

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000115

Gnomad OTH exome

AF:

0.000996

GnomAD4 exome

AF:

0.000960

AC:

1397

AN:

1455396

Hom.:

Cov.:

AF XY:

0.000809

AC XY:

586

AN XY:

724310

show subpopulations

Gnomad4 AFR exome

AF:

0.0322

Gnomad4 AMR exome

AF:

0.00229

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000815

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000687

Gnomad4 OTH exome

AF:

0.00223

GnomAD4 genome

AF:

0.00902

AC:

1374

AN:

152348

Hom.:

Cov.:

AF XY:

0.00840

AC XY:

626

AN XY:

74500

show subpopulations

Gnomad4 AFR

AF:

0.0306

Gnomad4 AMR

AF:

0.00490

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000132

Gnomad4 OTH

AF:

0.00804

Alfa

AF:

0.00230

Hom.:

Bravo

AF:

0.0115

ESP6500AA

AF:

0.0286

AC:

105

ESP6500EA

AF:

0.000122

AC:

ExAC

AF:

0.00284

AC:

343

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.0000546

EpiControl

AF:

0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

TOP6BL-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Apr 18, 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

AlphaMissense

Benign

0.077

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.45

CADD

Benign

0.36

DANN

Benign

0.61

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.017

LIST_S2

Benign

0.65

T;T;T;T;T

MetaRNN

Benign

0.0034

T;T;T;T;T

MetaSVM

Benign

-0.97

MutationTaster

Benign

0.58

D;D;D;D;D;D

PROVEAN

Benign

-0.58

N;N;N;.;N

REVEL

Benign

0.10

Sift

Benign

1.0

T;T;T;.;T

Sift4G

Benign

0.67

.;.;T;.;T

Vest4

0.24, 0.31

MVP

0.11

MPC

0.079

ClinPred

0.00088

GERP RS

-5.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

gMVP

0.044

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

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