Variant rs11230562 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_006725.5(CD6):c.650C>T(p.Thr217Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.206 in 1,606,434 control chromosomes in the GnomAD database, including 38,470 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.16 ( 2685 hom., cov: 34)

Exomes 𝑓: 0.21 ( 35785 hom. )

Consequence

CD6
NM_006725.5 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.764

Variant links:

Genes affected

CD6 (HGNC:1691): (CD6 molecule) This gene encodes a protein found on the outer membrane of T-lymphocytes as well as some other immune cells. The encoded protein contains three scavenger receptor cysteine-rich (SRCR) domains and a binding site for an activated leukocyte cell adhesion molecule. The gene product is important for continuation of T cell activation. This gene may be associated with susceptibility to multiple sclerosis (PMID: 19525953, 21849685). Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2011]

CD6 links:

CD6 (HGNC:):

CD6 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.005012661).

BP6

Variant 11-61008714-C-T is Benign according to our data. Variant chr11-61008714-C-T is described in ClinVar as [Benign]. Clinvar id is 3056065.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.225 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CD6	NM_006725.5 linkuse as main transcript	c.650C>T	p.Thr217Met	missense_variant	4/13	ENST00000313421.11	NP_006716.3	P30203-1Q8N4Q7Q6AZ88

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CD6	ENST00000313421.11 linkuse as main transcript	c.650C>T	p.Thr217Met	missense_variant	4/13	1	NM_006725.5	ENSP00000323280.7		P30203-1

Frequencies

GnomAD3 genomes

AF:

0.159

AC:

24160

AN:

152160

Hom.:

2685

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0437

Gnomad AMI

AF:

0.262

Gnomad AMR

AF:

0.154

Gnomad ASJ

AF:

0.426

Gnomad EAS

AF:

0.0225

Gnomad SAS

AF:

0.0714

Gnomad FIN

AF:

0.167

Gnomad MID

AF:

0.320

Gnomad NFE

AF:

0.228

Gnomad OTH

AF:

0.206

GnomAD3 exomes

AF:

0.171

AC:

39518

AN:

230678

Hom.:

4445

AF XY:

0.174

AC XY:

21892

AN XY:

125964

show subpopulations

Gnomad AFR exome

AF:

0.0430

Gnomad AMR exome

AF:

0.113

Gnomad ASJ exome

AF:

0.430

Gnomad EAS exome

AF:

0.0248

Gnomad SAS exome

AF:

0.0746

Gnomad FIN exome

AF:

0.172

Gnomad NFE exome

AF:

0.234

Gnomad OTH exome

AF:

0.223

GnomAD4 exome

AF:

0.211

AC:

306953

AN:

1454156

Hom.:

35785

Cov.:

AF XY:

0.209

AC XY:

151022

AN XY:

722760

show subpopulations

Gnomad4 AFR exome

AF:

0.0375

Gnomad4 AMR exome

AF:

0.118

Gnomad4 ASJ exome

AF:

0.429

Gnomad4 EAS exome

AF:

0.0237

Gnomad4 SAS exome

AF:

0.0776

Gnomad4 FIN exome

AF:

0.173

Gnomad4 NFE exome

AF:

0.233

Gnomad4 OTH exome

AF:

0.210

GnomAD4 genome

AF:

0.159

AC:

24145

AN:

152278

Hom.:

2685

Cov.:

AF XY:

0.155

AC XY:

11576

AN XY:

74460

show subpopulations

Gnomad4 AFR

AF:

0.0437

Gnomad4 AMR

AF:

0.154

Gnomad4 ASJ

AF:

0.426

Gnomad4 EAS

AF:

0.0224

Gnomad4 SAS

AF:

0.0718

Gnomad4 FIN

AF:

0.167

Gnomad4 NFE

AF:

0.228

Gnomad4 OTH

AF:

0.203

Alfa

AF:

0.230

Hom.:

3938

Bravo

AF:

0.156

TwinsUK

AF:

0.242

AC:

899

ALSPAC

AF:

0.229

AC:

883

ESP6500AA

AF:

0.0542

AC:

238

ESP6500EA

AF:

0.238

AC:

2045

ExAC

AF:

0.161

AC:

19349

Asia WGS

AF:

0.0540

AC:

189

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

CD6-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 22, 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

0.14

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.49

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.028

T;T;.;.;.

Eigen

Benign

-0.34

Eigen_PC

Benign

-0.52

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.11

T;T;T;T;T

MetaRNN

Benign

0.0050

T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.66

N;.;.;N;N

PrimateAI

Benign

0.38

PROVEAN

Uncertain

-2.5

N;N;D;N;N

REVEL

Benign

0.046

Sift

Uncertain

0.0040

D;D;D;D;D

Sift4G

Uncertain

0.010

D;D;D;D;D

Polyphen

1.0

D;.;P;D;D

Vest4

0.075

MPC

2.0

ClinPred

0.012

GERP RS

0.67

Varity_R

0.20

gMVP

0.68

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