Variant 11-66599487-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6BP7BS2

The NM_005125.2(CCS):c.279G>T(p.Leu93=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0103 in 1,546,340 control chromosomes in the GnomAD database, including 108 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.0066 ( 6 hom., cov: 31)

Exomes 𝑓: 0.011 ( 102 hom. )

Consequence

CCS
NM_005125.2 synonymous

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 1.53

Variant links:

Genes affected

CCS (HGNC:1613): (copper chaperone for superoxide dismutase) Copper chaperone for superoxide dismutase specifically delivers Cu to copper/zinc superoxide dismutase and may activate copper/zinc superoxide dismutase through direct insertion of the Cu cofactor. [provided by RefSeq, Jul 2008]

CCS links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.53).

BP6

Variant 11-66599487-G-T is Benign according to our data. Variant chr11-66599487-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 3041567.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=1.53 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCS	NM_005125.2 linkuse as main transcript	c.279G>T	p.Leu93=	synonymous_variant	4/8	ENST00000533244.6	NP_005116.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCS	ENST00000533244.6 linkuse as main transcript	c.279G>T	p.Leu93=	synonymous_variant	4/8	1	NM_005125.2	ENSP00000436318	P1

Frequencies

GnomAD3 genomes

AF:

0.00662

AC:

1006

AN:

152072

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00188

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00708

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00104

Gnomad FIN

AF:

0.00866

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0105

Gnomad OTH

AF:

0.00384

GnomAD3 exomes

AF:

0.00630

AC:

1233

AN:

195792

Hom.:

AF XY:

0.00620

AC XY:

664

AN XY:

107032

show subpopulations

Gnomad AFR exome

AF:

0.00128

Gnomad AMR exome

AF:

0.00331

Gnomad ASJ exome

AF:

0.000164

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00168

Gnomad FIN exome

AF:

0.00808

Gnomad NFE exome

AF:

0.00975

Gnomad OTH exome

AF:

0.00635

GnomAD4 exome

AF:

0.0107

AC:

14864

AN:

1394150

Hom.:

102

Cov.:

AF XY:

0.0105

AC XY:

7241

AN XY:

688700

show subpopulations

Gnomad4 AFR exome

AF:

0.00142

Gnomad4 AMR exome

AF:

0.00347

Gnomad4 ASJ exome

AF:

0.0000445

Gnomad4 EAS exome

AF:

0.0000262

Gnomad4 SAS exome

AF:

0.00188

Gnomad4 FIN exome

AF:

0.00808

Gnomad4 NFE exome

AF:

0.0127

Gnomad4 OTH exome

AF:

0.00789

GnomAD4 genome

AF:

0.00661

AC:

1006

AN:

152190

Hom.:

Cov.:

AF XY:

0.00637

AC XY:

474

AN XY:

74392

show subpopulations

Gnomad4 AFR

AF:

0.00188

Gnomad4 AMR

AF:

0.00707

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00104

Gnomad4 FIN

AF:

0.00866

Gnomad4 NFE

AF:

0.0105

Gnomad4 OTH

AF:

0.00380

Alfa

AF:

0.00758

Hom.:

Bravo

AF:

0.00612

Asia WGS

AF:

0.00115

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

CCS-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Mar 02, 2020

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

-0.53

CADD

Benign

0.80

DANN

Benign

0.47

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.6

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