11-66599487-G-T

Variant names:

• chr11-66599487-G-T
• rs61731811
• NM_005125.2:c.279G>T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6 BP7 BS2

The NM_005125.2(CCS):​c.279G>T​(p.Leu93Leu) 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
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: 1.53

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]

ACMG classification

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 rank	MANE	Protein	UniProt
CCS	NM_005125.2	c.279G>T	p.Leu93Leu	synonymous_variant	Exon 4 of 8	ENST00000533244.6	NP_005116.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCS	ENST00000533244.6	c.279G>T	p.Leu93Leu	synonymous_variant	Exon 4 of 8	1	NM_005125.2	ENSP00000436318.1

Frequencies

GnomAD3 genomes AF: 0.00662 AC: 1006 AN: 152072 Hom.: 6 Cov.: 31

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.: 7 AF XY: 0.00620 AC XY: 664 AN XY: 107032

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.: 31 AF XY: 0.0105 AC XY: 7241 AN XY: 688700

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.: 6 Cov.: 31 AF XY: 0.00637 AC XY: 474 AN XY: 74392

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.: 0

Bravo AF: 0.00612

Asia WGS AF: 0.00115 AC: 4 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

CCS-related disorder Benign:1

Mar 02, 2020

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

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

Other links and lift over

dbSNP: rs61731811; hg19: chr11-66366958; COSMIC: COSV59580787; COSMIC: COSV59580787;