Variant 11-66744924-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.-30+5T>C variant causes a splice donor 5th base, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0099 in 1,254,476 control chromosomes in the GnomAD database, including 78 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.0073 ( 8 hom., cov: 30)

Exomes 𝑓: 0.010 ( 70 hom. )

Consequence

C11orf80
NM_001302084.2 splice_donor_5th_base, intron

Scores

Splicing: ADA: 0.003980

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.360

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 (BayesDel_noAF=-0.5).

BP6

Variant 11-66744924-T-C is Benign according to our data. Variant chr11-66744924-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 3055893.Status of the report is no_assertion_criteria_provided, 0 stars.

BS1

Variant frequency is greater than expected in population sas. gnomad4_exome allele frequency = 0.0103 (11303/1102516) while in subpopulation SAS AF= 0.0211 (462/21874). AF 95% confidence interval is 0.0195. There are 70 homozygotes in gnomad4_exome. There are 5414 alleles in male gnomad4_exome subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
C11orf80	NM_001302084.2 linkuse as main transcript	c.-30+5T>C		splice_donor_5th_base_variant, intron_variant		ENST00000540737.7	NP_001289013.1
C11orf80	NM_024650.3 linkuse as main transcript	c.177+5T>C		splice_donor_5th_base_variant, intron_variant			NP_078926.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
C11orf80	ENST00000540737.7 linkuse as main transcript	c.-30+5T>C		splice_donor_5th_base_variant, intron_variant		2	NM_001302084.2	ENSP00000444319	A2

Frequencies

GnomAD3 genomes

AF:

0.00732

AC:

1112

AN:

151842

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00181

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00295

Gnomad ASJ

AF:

0.00778

Gnomad EAS

AF:

0.000194

Gnomad SAS

AF:

0.0166

Gnomad FIN

AF:

0.0187

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.00995

Gnomad OTH

AF:

0.00384

GnomAD3 exomes

AF:

0.0135

AC:

262

AN:

19442

Hom.:

AF XY:

0.0140

AC XY:

133

AN XY:

9486

show subpopulations

Gnomad AFR exome

AF:

0.00105

Gnomad AMR exome

AF:

0.00323

Gnomad ASJ exome

AF:

0.0161

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0196

Gnomad FIN exome

AF:

0.0184

Gnomad NFE exome

AF:

0.00991

Gnomad OTH exome

AF:

0.00719

GnomAD4 exome

AF:

0.0103

AC:

11303

AN:

1102516

Hom.:

Cov.:

AF XY:

0.0104

AC XY:

5414

AN XY:

522804

show subpopulations

Gnomad4 AFR exome

AF:

0.00113

Gnomad4 AMR exome

AF:

0.00460

Gnomad4 ASJ exome

AF:

0.00716

Gnomad4 EAS exome

AF:

0.0000753

Gnomad4 SAS exome

AF:

0.0211

Gnomad4 FIN exome

AF:

0.0204

Gnomad4 NFE exome

AF:

0.0103

Gnomad4 OTH exome

AF:

0.00801

GnomAD4 genome

AF:

0.00733

AC:

1114

AN:

151960

Hom.:

Cov.:

AF XY:

0.00778

AC XY:

578

AN XY:

74296

show subpopulations

Gnomad4 AFR

AF:

0.00181

Gnomad4 AMR

AF:

0.00295

Gnomad4 ASJ

AF:

0.00778

Gnomad4 EAS

AF:

0.000194

Gnomad4 SAS

AF:

0.0170

Gnomad4 FIN

AF:

0.0187

Gnomad4 NFE

AF:

0.00995

Gnomad4 OTH

AF:

0.00380

Alfa

AF:

0.00835

Hom.:

Bravo

AF:

0.00600

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

TOP6BL-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 20, 2019

This variant is classified as likely 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

-0.50

CADD

Benign

DANN

Benign

0.79

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0040

dbscSNV1_RF

Benign

0.088

SpliceAI score (max)

0.12

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