Variant 11-66605834-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BA1

The NM_005125.2(CCS):c.804G>A(p.Ala268=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.152 in 1,563,720 control chromosomes in the GnomAD database, including 19,585 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.11 ( 1259 hom., cov: 32)

Exomes 𝑓: 0.16 ( 18326 hom. )

Consequence

CCS
NM_005125.2 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.321

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

BP6

Variant 11-66605834-G-A is Benign according to our data. Variant chr11-66605834-G-A is described in ClinVar as [Benign]. Clinvar id is 3057199.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=-0.321 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.162 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCS	NM_005125.2 linkuse as main transcript	c.804G>A	p.Ala268=	synonymous_variant	8/8	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.804G>A	p.Ala268=	synonymous_variant	8/8	1	NM_005125.2	ENSP00000436318	P1

Frequencies

GnomAD3 genomes

AF:

0.113

AC:

17156

AN:

152158

Hom.:

1259

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0311

Gnomad AMI

AF:

0.195

Gnomad AMR

AF:

0.0819

Gnomad ASJ

AF:

0.110

Gnomad EAS

AF:

0.0287

Gnomad SAS

AF:

0.137

Gnomad FIN

AF:

0.170

Gnomad MID

AF:

0.101

Gnomad NFE

AF:

0.165

Gnomad OTH

AF:

0.108

GnomAD3 exomes

AF:

0.127

AC:

26230

AN:

207144

Hom.:

1896

AF XY:

0.132

AC XY:

14694

AN XY:

110914

show subpopulations

Gnomad AFR exome

AF:

0.0279

Gnomad AMR exome

AF:

0.0742

Gnomad ASJ exome

AF:

0.134

Gnomad EAS exome

AF:

0.0293

Gnomad SAS exome

AF:

0.155

Gnomad FIN exome

AF:

0.171

Gnomad NFE exome

AF:

0.159

Gnomad OTH exome

AF:

0.129

GnomAD4 exome

AF:

0.156

AC:

220693

AN:

1411444

Hom.:

18326

Cov.:

AF XY:

0.157

AC XY:

109499

AN XY:

697604

show subpopulations

Gnomad4 AFR exome

AF:

0.0242

Gnomad4 AMR exome

AF:

0.0729

Gnomad4 ASJ exome

AF:

0.124

Gnomad4 EAS exome

AF:

0.0236

Gnomad4 SAS exome

AF:

0.154

Gnomad4 FIN exome

AF:

0.167

Gnomad4 NFE exome

AF:

0.169

Gnomad4 OTH exome

AF:

0.140

GnomAD4 genome

AF:

0.113

AC:

17152

AN:

152276

Hom.:

1259

Cov.:

AF XY:

0.112

AC XY:

8352

AN XY:

74458

show subpopulations

Gnomad4 AFR

AF:

0.0310

Gnomad4 AMR

AF:

0.0818

Gnomad4 ASJ

AF:

0.110

Gnomad4 EAS

AF:

0.0286

Gnomad4 SAS

AF:

0.136

Gnomad4 FIN

AF:

0.170

Gnomad4 NFE

AF:

0.165

Gnomad4 OTH

AF:

0.107

Alfa

AF:

0.124

Hom.:

492

Bravo

AF:

0.101

Asia WGS

AF:

0.0700

AC:

247

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

CCS-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Nov 12, 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

-0.78

CADD

Benign

5.3

DANN

Benign

0.50

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